Implant comprising a calcium salt-containing composite powder having microstructured particles

ABSTRACT

Implant comprising composite powder with microstructured particles, obtained by a process in which large particles are bonded to small particles, wherein
         the large particles have a mean particle diameter in the range from 10 μm to 10 mm,   the large particles comprise at least one polymer,   the small particles are arranged on the surface of the large particles and/or are non-homogeneously spread within the large particles,   the small particles comprise a calcium salt,   the small particles have a mean particle size in the range from 0.01 μm to 1.0 mm,
 
wherein the particles of the composite powder have a mean particle size d50 in the range from 10 μm to less than 200 μm and the fine fraction of the composite powder is less than 50 vol %.
       

     Therefore, the subject matter of the invention further are implants obtained by selective laser sintering of a composition comprising a composite powder, especially as an implant for applications in the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as of hand, foot, thorax, costal and shoulder surgery.

The present invention relates to an implant comprising composite powdercontaining calcium salt obtained by selective laser sintering,especially to implants for use in the field of neuro, oral, maxillary,facial, ear, nose and throat surgery as well as hand, foot, thorax,costal and shoulder surgery.

The invention does not relate to the preparation of the startingmaterial for the implant, nor to the use for purposes other than theproduction of an implant, especially one that is prepared for use in thefield of neuro, oral, maxillary, facial, ear, nose and throat surgery aswell as hand, foot, thorax, costal and shoulder surgery.

Calcium carbonate, CaCO₃, is a calcium salt of the carbonic acid whichtoday is in use in various fields of daily life. It is used especiallyas an additive or modifier in paper, dyes, plastics, inks, adhesives andpharmaceuticals. In plastics, calcium carbonate preferentially serves asfiller to replace the comparatively expensive polymer.

Also, composite materials are known already and denote a materialconsisting of two or more bonded materials which has material propertiesother than its individual components. Concerning the properties of thecomposite materials, the material properties and the geometry of thecomponents are important. In particular, effects of size frequently playa role. The bonding is usually made by adhesion or form closure or by acombination of both.

Further, also microstructured composite particles containing calciumsalts, especially calcium carbonate, are known per se already.

For example, WO 2012/126600 A2 discloses microstructured compositeparticles obtainable by a method in which large particles are bonded tosmall particles, wherein

-   -   the large particles have a mean particle diameter within the        range from 0.1μ to 10 mm,    -   the mean particle diameter of the small particles is no more        than 1/10 of the mean particle diameter of the large particles,    -   the large particles comprise at least one polymer,    -   the small particles comprise calcium carbonate,    -   the small particles are disposed on the surface of the large        particles and/or are non-homogeneously spread within the large        particles,        wherein the small particles comprise precipitated calcium        carbonate particles having a mean particle size within the range        from 0.01 μm to 1.0 mm.

Further, WO 2012/126600 A2 describes microstructured composite particlesobtainable by a method in which large particles are connected to smallparticles, wherein

-   -   the large particles have a mean particle diameter within the        range from 0.1 μm to 10 mm,    -   the mean particle diameter of the small particles is no more        than 1/10 of the mean particle diameter of the large particles,    -   the large particles comprise at least one polymer,    -   the small particles comprise at least one calcium salt,    -   the small particles are disposed on the surface of the large        particles and/or are non-homogeneously spread within the large        particles,        wherein the large particles comprise at least one absorbable        polyester having a number average molecular weight within the        range from 500 g/mol to 1,000,000 g/mol.

The composite particles shown in WO 2012/126600 A2 are intended to besuited mainly as an additive, especially as a polymer additive, as anadmixture or starting material for the production of components, for usein medical engineering and/or in microtechnology and/or for theproduction of foamed objects. The method of selective laser sintering(SLM method) is mentioned inter alia in the document.

However, for selective laser sintering more properly suited materialsare desired. One drawback of the composite particles of WO 2012/126600A2 especially is the poor flowability thereof which can only partiallybe reduced even when flowing aids are used. Additions of said flowingaids are not beneficial, above all, to the production of implants, asthey usually have a detrimental effect on the properties of theresulting implant, especially on its biocompatibility andbiodegradability. Further, transportation to the laser sintering plantis impeded by the poor flowability.

When producing components by laser sintering making use of the materialsof WO 2012/126600 A2, the following additional problems will arise.Although ground composite particles can be sintered, the surface qualityand surface finish as well as the component density of the resultingcomponents are not fully satisfactory. Especially better shrinkingbehavior and better dimensional stability of the resulting components aswell as better heat conductivity outside the laser-treated area would bedesirable. Moreover, a more efficient production process of componentswould be desirable. In particular, an enhancement for implants,especially for the field of neuro, oral, maxillary, facial, ear, noseand throat surgery as well as of hand, foot, thorax, costal and shouldersurgery would be desirable.

Against this background, it is the object of the present invention tomake available a better implant than before. Especially a materialexhibiting improved laser sintering properties which has especially animproved flowability, during laser sintering enables components ofimproved surface quality and surface finish as well as improvedcomponent density to be produced and shows especially better shrinkingbehavior and improved dimensional stability of the resulting componentsas well as better heat conductivity outside the laser-treated areashould be used for an implant. In addition, a more efficient productionprocess of such implants is requested.

This object as well as further objects which are not concretized but canbe directly derived from the foregoing context are achieved by providingan implant made from a composite powder including all features of thepresent claim 1. The subclaims related back to claim 1 describeespecially expedient variants. The use claim relates to an especiallyexpedient application of the composite powder according to the inventionfor producing an implant, especially for the field of neuro, oral,maxillary, facial, ear, nose and throat surgery as well as of hand,foot, thorax, costal and shoulder surgery. Furthermore, an especiallyadvantageous implant is protected which is obtained by selective lasersintering of a composition containing said composite powder and which isespecially configured as an implant for applications in the field ofneuro, oral, maxillary, facial, ear, nose and throat surgery as well asof hand, foot, thorax, costal and shoulder surgery.

Providing a composite powder comprising microstructured particlesobtainable by a process in which large particles are bonded to smallparticles, wherein

-   -   the large particles have a mean particle diameter in the range        from 10 μm to 10 mm,    -   the large particles comprise at least one polymer,    -   the small particles are disposed on the surface of the large        particles and/or are non-homogeneously spread within the large        particles,    -   the small particles comprise at least one calcium salt,    -   the small particles have a mean particle size in the range from        0.01 μm to 1.0 mm,        wherein the particles of the composite powder have a mean        particle size d₅₀ in the range from 10 μm to less than 200 μm        and the fine fraction of the composite powder is less than 50        vol %, will not succeed in an easily foreseeable manner in        making available a composite powder containing calcium salt and        including microstructured particles having improved properties        which are excellently suited especially for use in laser        sintering methods. The composite powder according to the        invention has improved flowability, during laser sintering        enables components having improved surface quality and surface        finish as well as improved component density to be produced. At        the same time, the resulting components exhibit better shrinking        behavior and improved dimensional stability. Further, better        heat conductivity outside the laser-treated area can be noted.

Moreover, said composite powder allows for more efficient production ofimplants, especially according to the laser sintering method. The meltflow of the melt obtainable using the composite powder according to theinvention is significantly increased (enhanced). The composite powderaccording to the invention can be better processed especially accordingto the SLM method, compared to conventional materials, and enables asignificantly better layer structure in the SLM method. The componentsobtainable according to the SLM method using the composite powderaccording to the invention excel by extremely high quality and, comparedto components produced according to the SLM method using conventionalmaterials, show definitely fewer defects, increased component density,preferably higher than 95%, especially higher than 97%, as well as lessporosity. At the same time, the content of degradation products in theresulting components is significantly lower and the cell compatibilityof the components is extremely high.

The other properties of the implants obtainable in this way areexcellent, too. The implants show very good mechanical properties aswell as excellent pH stability. At the same time, the biocompatibilityof the products is significantly enhanced. Comparable products are notobtainable when using the pure polymers, in particular as respectivepolymer powders which might be processed according to the SLM method arenot known.

It is another advantage of the present invention that the properties ofsaid composite powder, especially the flow properties of the compositepowder, can be specifically controlled and adjusted by the input and theproperties of the large particles and the small particles, especially bythe properties of the calcium salt, above all by the particle size ofthe calcium salt particles, as well as by the quantity of the calciumsalt particles. Moreover, by sizing the composite powder especially thecalcium salt content, above all the calcium carbonate content, of thecomposite powder and the flow properties of the composite powder can bevaried and specifically adapted to the respective application.

Especially in combination with polylactide as polymer the followingadvantages are resulting in accordance with the invention.

Using the said composite powder, degradable implants, havingcontrollable absorption kinetics and adjustable mechanical propertiescan be produced. Polylactides which are preferably contained in thecomposite powder are biodegradable polymers on the basis of lactic acid.In the organism polylactides are degraded by hydrolysis. Calcium salts,especially calcium phosphate and calcium carbonate, are mineralmaterials based on calcium and are degraded in the body by the naturalregeneration process of the bone. Calcium carbonate has the particularlyadvantageous property to buffer the acidic milieu which may be toxic tobone cells when the polylactides are degraded. As compared to calciumphosphate (pH 4), calcium carbonate buffers already at a pH value ofabout 7, i.e. close to the physiological value of 7.4. The time untilcomplete degradation can be adapted via the length of molecular chainsand the chemical composition of the polymer, especially of thepolylactide. This is similarly possible for the mechanical properties ofthe polymer.

Said composite powder may be processed to form implant structures withthe aid of the generative production method of Selective Laser Melting(SLM). Here a specific adaptation of the material and the productionmethod to each other and to the medical requirements is possible. Theuse of the generative production and the accompanying freedom ofgeometry offers the option to provide the implant with an internal andopen pore structure corresponding to the surgeon's requests whichensures continuous supply of the implant. Moreover, generativelyindividually adapted implants as required for supplying large-area bonedefects in the craniofacial area can be quickly and economicallymanufactured. The advantage of said composition for processing by meansof SLM especially resides in the fact that the polymer can be melted bylaser radiation at relatively low temperatures, preferably less than300° C., and the inhibiting calcium carbonate particles remain thermallystable at said temperatures. By customized synthesis of said compositepowder, the calcium salt particles, especially the calcium carbonateparticles, thus can be homogeneously embedded within the entire volumeof the implant in a matrix of polylactide without thermal damage by thelaser radiation. The strength of the implant is determined, on the onehand, by the polylactide matrix and, on the other hand, by themorphology of the calcium salt particles, especially the calciumcarbonate particles, as well as, of preference, also by the mixing ratioof the components used. The implants furthermore are bioactive, as theyactively stimulate the surrounding bone tissue to osteogenesis andreplacement of the skeleton structure (implant) via the selection ofmaterial and the subsequent coating with a growth-stimulating protein(rhBMP-2).

The substantial benefits of the implants made of said composite powder,generatively produced by means of SLM especially are as follows:

-   -   The use of biodegradable osteoconductive materials actively        stimulates bone to grow through the implant and, even for        large-area defects, achieves complete degradation while bone        forms completely newly in the bone defect to be repaired. Due to        the interconnecting pore structure the BMP coating can be active        in the entire “volume” of the implant.    -   Sprouting of bone tissue: Introduction of a proper pore        structure favors sprouting of new bone tissue into the implant.        The generative production process helps to introduce a defined        pore structure into the components in a reproducible manner.    -   The suggested solution further offers the advantage to prevent        medical complications of long-term implants at best, to increase        at best the patient's wellbeing by avoiding permanent foreign        body sensation, and—above all for children and young persons—to        realize at best an “adaptive” implant.    -   Optimum buffering: By the use of calcium salts, especially of        calcium carbonate, the acid degradation of the polylactide        material is buffered already at a pH value of about 7 so that        the forming acid milieu in the environment of the implant and        thus inflammatory or cytotoxic action can be prevented.        Moreover, degradation processes of the polymer, especially of        the lactic acid polymer, are suppressed at best.    -   High strength: The SLM process produces a completely fused        compound and thus high component density and strength, thus        allowing even large-area defects to be repaired by individually        adapted implants made from biodegradable material and open pore        structure.

Accordingly, the subject matter of the present invention is a compositepowder comprising microstructured particles (composite powder) in animplant, the composite powder being obtainable by a method in whichlarge particles are bonded to small particles.

In the present invention, microstructure refers to the microscopicproperties of a material. They include, inter alia, the resolvable finestructure and the structure. In liquids as well as in gases, the latterare not provided. Here the individual atoms or molecules are in adisordered state. Amorphous solids mostly have a structural short-rangeorder in the area of the neighboring atoms but no long-range order.Crystalline solids, on the other hand, have an ordered grid structurenot only in the short-range area but also in the long-range area.

Within the scope of the present invention, the large particles compriseat least one polymer which basically is not subject to any furtherrestrictions. However, preferably it is a thermoplastic polymer,appropriately a biopolymer, a rubber, especially natural rubber orsynthetic rubber, and/or a polyurethane.

The term “thermoplastic polymer” in this context refers to a plasticwhich can be (thermoplastically) deformed within a specific temperaturerange, preferably within the range from 25° C. to 350° C. This operationis reversible, i.e. it can be repeated any time by cooling and reheatingto the molten state, unless the so-called thermal decomposition of thematerial starts by overheating. By this feature, thermoplastic polymersdiffer from the thermosetting plastics and elastomers.

The term “biopolymer” denotes a material consisting of biogenic rawmaterials (renewable raw materials) and/or being biodegradable (biogenicand/or biodegradable polymer). This term thus covers bio-basedbiopolymers which are or are not biodegradable as well aspetroleum-based polymers which are biodegradable. Thus, a delimitationis made against the conventional petroleum-based materials and, resp.,plastics which are not biodegradable such as e.g. polyethylene (PE),polypropylene (PP) and polyvinylchloride (PVC).

The term “rubber” denotes high-molecular non-crosslinked polymericmaterial having rubber-elastic properties at room temperature (25° C.).At higher temperatures or under the influence of deforming forces,rubber shows increasingly viscous flow and thus enables to be reformedunder appropriate conditions.

Rubber-elastic behavior is characterized by a relatively low shearmodulus of rather little temperature dependency. It is caused by changesof entropy. By stretching the rubber-elastic material is forced to adopta more ordered configuration resulting in a decrease of entropy. Afterremoving force, the polymers therefore return to their original positionand the entropy increases again.

The term “polyurethane” (PU, DIN abbreviation: PUR) denotes a plastic orsynthetic resin which is formed by the polyaddition reaction of diols orpolyols with poly-isocyanates. The urethane group is characteristic of apolyurethane.

Within the scope of the present invention, it is especially preferred touse thermoplastic polymers. Especially suited polymers include thefollowing polymers: acrylonitrile-ethylene-propylene-(diene)-styrenecopolymer, acrylonitrile-methacrylate copolymer, acrylonitrile-methylmethacrylate copolymer, acrylonitrile-chlorinated polyethylene-styrenecopolymer, acrylonitrile-butadiene-styrene copolymer,acrylonitrile-ethylene-propylene-styrene copolymer, aromatic polyesters,acrylonitrile-styrene-acrylic ester copolymer, butadiene-styrenecopolymer, cellulose acetate, cellulose aceto butyrate, cellulose acetopropionate, hydrated cellulose, carboxymethyl cellulose, cellulosenitrate, cellulose propionate, cellulose triacetate, polyvinyl chloride,ethylene-acrylic acid copolymer, ethylene-butyl acrylate copolymer,ethylene-chlorotrifluoroethylene copolymer, ethylene-ethyl acrylatecopolymer, ethylene-methacrylate copolymer, ethylene-methacrylic acidcopolymer, ethylene-tetrafluoroethylene copolymer, ethylene-vinylalcohol copolymer, ethylene-butene copolymer, ethyl cellulose,polystyrene, poly fluoroethylene propylene, methylmethacrylate-acrylonitrile-butadiene-styrene copolymer, methylmethacrylate-butadiene-styrene copolymer, methyl cellulose, polyamide11, polyamide 12, polyamide 46, polyamide 6, polyamide 6-3-T, polyamide6-terephthalic acid copolymer, polyamide 66, polyamide 69, polyamide610, polyamide 612, polyamide 61, polyamide MXD 6, polyamide PDA-T,polyamide, polyaryl ether, polyaryl ether ketone, polyamide imide,polyaryl amide, polyamine bismaleimide, polyarylates, polybutene-1,polybutyl acrylate, polybenzimidazole, polybismaleimide, polyoxadiazobenzimidazole, polybutylene terephthalate, polycarbonate,polychlorotrifluoroethylene, polyethylene, polyester carbonate, polyarylether ketone, polyetherether ketone, polyether imide, polyether ketone,polyethylene oxide, polyaryl ether sulf one, polyethylene terephthalate,polyimide, polyisobutylene, polyisocyanurate, polyimide sulf one,polymethacryl imide, polymethacrylate, poly-4-methylpentene-1,polyacetal, polypropylene, polyphenylene oxide, polypropylene oxide,polyphenylene sulfide, polyphenylene sulf one, polystyrene, polysulfone, polytetrafluoroethylene, polyurethane, polyvinyl acetate, polyvinylalcohol, polyvinyl butyral, polyvinyl chloride, polyvinylidene chloride,polyvinylidene fluoride, polyvinyl fluoride, polyvinyl methyl ether,polyvinyl pyrrolidone, styrene-butadiene copolymer, styrene-isoprenecopolymer, styrene-maleic acid anhydride copolymer, styrene-maleic acidanhydride-butadiene copolymer, styrene-methyl methacrylate copolymer,styrene methyl styrene copolymer, styrene-acrylonitrile copolymer, vinylchloride-ethylene copolymer, vinyl chloride-methacrylate copolymer,vinyl chloride-maleic acid anhydride copolymer, vinyl chloride-maleimidecopolymer, vinyl chloride-methyl methacrylate copolymer, vinylchloride-octyl acrylate copolymer, vinyl chloride-vinyl acetatecopolymer, vinyl chloride-vinylidene chloride copolymer and vinylchloride-vinylidene chloride-acrylonitrile copolymer.

Further, also the use of the following rubbers is especiallyadvantageous: naturally occurring polyisoprene, especiallycis-1,4-polyisoprene (natural rubber; NR) and trans-1,4-polyisoprene(gutta-percha), primarily natural rubber; nitrile rubber (copolymer ofbutadiene and acrylonitrile); poly(acrylonitrile-co-1,3-butadiene; NBR;so-called Buna N-rubber); butadiene rubber (polybutadiene; BR); acrylicrubber (polyacrylic rubber; ACM, ABR); fluorine rubber (FPM);styrene-butadiene rubber (copolymer of styrene and butadiene; SBR);styrene-isoprene-butadiene rubber (copolymer of styrene, isoprene andbutadiene; SIBR); polybutadiene; synthetic isoprene rubber(polyisoprene; IR), ethylene-propylene rubber (copolymer of ethylene andpropylene; EPM); ethylene-propylene-diene rubber (terpolymer ofethylene, propylene and a diene component; EPDM); butyl rubber(copolymer of isobutylene and isoprene; IIR); ethylene-vinyl acetaterubber (copolymer of ethylene and vinyl acetate; EVM);ethylene-methacrylate rubber (copolymer of ethylene and methacrylate;AEM); epoxy rubber such as polychloromethyl oxirane (epichlorohydrinpolymer; CO), ethylene oxide (oxirane)-chloromethyl oxirane(epichlorohydrin polymer; ECO), epichlorohydrin-ethylene oxide-allylglycidyl ether terpolymer (GECO), epichlorohydrin-allyl glycidyl ethercopolymer (GCO) and propylene oxide-allyl glycidyl ether copolymer(GPO); polynorbornene rubber (polymer of bicyclo[2.2.1]hept-2-en(2-norbornene); PNR); polyalkenylene (polymer of cycloolefins); siliconerubber (Q) such as silicone rubber but with methyl substituents at thepolymer chain (MQ; e.g. dimethyl polysiloxane), silicone rubber withmethyl vinyl and vinyl substituent groups at the polymer chain (VMQ),silicone rubber with phenyl and methyl substituents at the polymer chain(PMQ), silicone rubber with fluorine and methyl groups at the polymerchain (FMQ), silicone rubber with fluorine, methyl and vinylsubstituents at the polymer chain (FVMQ); polyurethane rubber;polysulfide rubber; halogen butyl rubber such as bromine butyl rubber(BIIR) and chlorine butyl rubber (CIIR); chlorine polyethylene (CM);chlorine sulfonyl polyethylene (CSM); hydrated nitrile rubber (HNBR);and polyphosphazene.

Especially preferred nitrile rubbers include statistic terpolymers ofacrylonitrile, butadiene and a carboxylic acid such as methacrylic acid.In this context, the nitrile rubber preferably comprises the followingmain components, based on the total weight of the polymer: 15.0 wt.-% to42.0 wt.-% of acrylonitrile polymer; 1.0 wt.-% to 10.0 wt.-% ofcarboxylic acid and the remainder is mostly butadiene (e.g. 38.0 wt.-%to 75.0 wt.-%). Typically, the composition is: 20.0 wt.-% to 40.0 wt.-%of acrylonitrile polymer, 3.0 wt.-% to 8.0 wt.-% of carboxylic acid and40.0 wt.-% to 65.0 wt.-% or 67.0 wt.-% are butadiene. Especiallypreferred nitrile rubbers include a terpolymer of acrylonitrile,butadiene and a carboxylic acid in which the content of acrylonitrile isless than 35.0 wt.-% and the content of carboxylic acid is less than10.0 wt.-%, with the content of butadiene corresponding to theremainder. Even more preferred nitrile rubbers may comprise thefollowing quantities: 20.0 wt.-% to 30.0 wt.-% of acrylonitrile polymer,4.0 wt.-% to 6.0 wt.-% of carboxylic acid and most of the remainder isbutadiene.

The use of nitrogenous polymers, especially of polyamides, is especiallyfavorable within the scope of the present invention. Especiallypreferred are polyamide 11, polyamide 12, polyamide 46, polyamide 6,polyamide 6-3-T, polyamide 6-terephthalic acid copolymer, polyamide 66,polyamide 69, polyamide 610, polyamide 612, polyamide 61, polyamide MXD6 and/or polyamide PDA-T, especially polyamide 12.

Moreover, also ultrahigh-molecular polyethylenes (UHMWPE) are especiallybeneficial to the purposes of the present invention, especially thosehaving an average molar mass of more than 1000 kg/mol, preferably morethan 2000 kg/mol, especially preferred more than 3000 kg/mol, especiallymore than 5000 kg/mol. The average molecular weight favorably is no morethan 10000 kg/mol. The density of especially suited ultrahigh-molecularpolyethylenes is within the range from 0.94-0.99 g/cm³. Thecrystallinity of especially suited ultrahigh-molecular polyethylenes iswithin the range from 50% to 90%. The tensile strength of especiallysuited ultrahigh-molecular polyethylenes is within the range from 30N/mm² to 50 N/mm². The tensile E modulus of especially suitedultrahigh-molecular polyethylenes is within the range from 800 N/mm² to2700 N/mm². The melting range of especially suited ultrahigh-molecularpolyethylenes is within the range from 135° C. to 155° C.

Furthermore, also the use of absorbable polymers is especiallyexpedient. The term “resorption/absorption” (lat. resorbere=“to suck”)is understood to be the absorption of matter in biological systems,especially into the human organism. Of current interest are especiallythose materials which can be used to produce absorbable implants.

Absorbable polymers especially preferred according to the inventioncomprise repeated units of the lactic acid, the hydroxybutyric acidand/or the glycolic acid, of preference of the lactic acid and/or theglycolic acid, especially of the lactic acid. Polylactic acids areespecially preferred.

By “polylactic acid” (polylactides) polymers are understood which arestructured of lactic acid units. Said polylactic acids are usuallyprepared by condensation of lactic acids but are also obtained duringring-opening polymerization of lactides under suitable conditions.

Absorbable polymers especially suited according to the invention includepoly(glycolide-co-L-lactide), poly(L-lactide),poly(L-lactide-co-ε-caprolactone), poly(L-lactide-co-glycolide),poly(L-lactide-co-D,L-lactide), poly(D,L-lactide-co-glycolide) as wellas poly(dioxanone), wherein lactic acid polymers, especially poly-D-,poly-L- or poly-D,L-lactic acids, above all poly-L-lactic acids (PLLA)and poly-D,L-lactic acids, are especially preferred according to theinvention, wherein especially the use of poly-L-lactic acids (PLLA) isextraordinarily advantageous.

In accordance with the invention, poly-L-lactic acid (PLLA) preferablyhas the following structure

wherein n is an integer, preferably larger than 10.

Poly-D,L-lactic acid preferably has the following structure

wherein n is an integer, preferably larger than 10.

Lactic acid polymers suited for the purpose of the present inventionare, for example, commercially available by Evonik Nutrition & Care GmbHunder the brand names Resomer® GL 903, Resomer® L 206 S, Resomer® L 207S, Resomer® R 208 G, Resomer® L 209 S, Resomer® L 210, Resomer® L 210 S,Resomer® LC 703 S, Resomer® LG 824 S, Resomer® LG 855 S, Resomer® LG 857S, Resomer® LR 704 S, Resomer® LR 706 S, Resomer® LR 708, Resomer® LR927 S, Resomer® RG 509 S and Resomer® X 206 S.

Absorbable polymers especially beneficial to the purposes of the presentinvention, which preferably are absorbable polyesters, preferably lacticacid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lacticacids, especially poly-L-lactic acids, have a number average molecularweight (Mn), preferably determined by gel permeation chromatographyagainst narrowly distributed polystyrene standards or by final grouptitration, of more than 500 g/mol, preferably more than 1,000 g/mol,especially preferred more than 5,000 g/mol, appropriately more than10,000 g/mol, especially more than 25,000 g/mol. On the other hand, thenumber average of preferred absorbable polymers is less than 1,000,000g/mol, appropriately less than 500,000 g/mol, favorably less than100,000 g/mol, especially not exceeding 50,000 g/mol. A number averagemolecular weight within the range from 500 g/mol to 50,000 g/mol hasparticularly proven within the scope of the present invention.

The weight average molecular weight (Mw) of preferred absorbablepolymers, which preferably are absorbable polyesters, favorably lacticacid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lacticacids, especially poly-L-lactic acids, preferably determined by gelpermeation chromatography against narrowly distributed polystyrenestandards, of preference ranges from 750 g/mol to 5,000,000 g/mol,preferably from 750 g/mol to 1,000,000 g/mol, especially preferred from750 g/mol to 500,000 g/mol, especially from 750 g/mol to 250,000 g/mol,and the polydispersity of said polymers favorably ranges from 1.5 to 5.

The inherent viscosity of especially suited absorbable polymers, whichpreferably are lactic acid polymers, especially preferred poly-D-,poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids,measured in chloroform at 25° C., 0.1% of polymer concentration, rangesfrom 0.3 dl/g to 8.0 dl/g, of preference from 0.5 dl/g to 7.0 dl/g,especially preferred from 0.8 dl/g to 2.0 dl/g, especially from 0.8 dl/gto 1.2 dl/g.

Further, the inherent viscosity of especially suited absorbablepolymers, which preferably are lactic acid polymers, especiallypreferred poly-D-, poly-L- or poly-D,L-lactic acids, especiallypoly-L-lactic acids, measured in hexafluoro-2-propanol at 30° C., 0.1%polymer concentration, ranges from 1.0 dl/g to 2.6 dl/g, especially from1.3 dl/g to 2.3 dl/g.

Within the scope of the present invention, moreover polymers, favorablythermoplastic polymers, of preference lactic acid polymers, especiallypreferred poly-D-, poly-L- or poly-D,L-lactic acids, especiallypoly-L-lactic acids, having a glass transition temperature of more than20° C., favorably more than 25° C., preferably more than 30° C.,especially preferred more than 35° C., especially more than 40° C., areextremely advantageous. Within the scope of an extraordinarily preferredembodiment of the present invention, the glass transition temperature ofthe polymer is within the range from 35° C. to 70° C., favorably withinthe range from 55° C. to 65° C., especially within the range from 60° C.to 65° C.

Furthermore, polymers, favorably thermoplastic polymers, of preferencelactic acid polymers, especially preferred poly-D-, poly-L- orpoly-D,L-lactic acids, especially poly-L-lactic acids, which exhibit amelting temperature of more than 50° C., favorably of at least 60° C.,preferably of more than 150° C., especially preferred within the rangefrom 130° C. to 210° C., especially within the range from 175° C. to195° C., are especially suited.

The glass temperature and the melting temperature of the polymer arepreferably established by means of differential scanning calorimetry,abbreviated to DSC. In this context, the following procedure hasespecially proven itself:

Carrying out DSC measurement under nitrogen on a Mettler-Toledo DSC 30S.Calibration is preferably carried out with indium. The measurements arepreferably carried out under dry oxygen-free nitrogen (flow rate:preferably 40 ml/min). The sample weight is preferably selected to bebetween 15 mg/g and 20 mg/g. The samples are initially heated from 0° C.to preferably a temperature above the melting temperature of the polymerto be tested, then cooled to 0° C. and a second time heated from 0° C.to said temperature at a heating rate of 10° C./min.

Polyamides, UHMWPE as well as absorbable polymers, above all absorbablepolyesters such as poly butyric acid, polyglycolic acid (PGA), lacticacid polymers (PLA) and lactic acid copolymers are especially preferredas thermoplastic polymers, with lactic acid polymers and lactic acidcopolymers, especially poly-L-lactide, poly-D,L-lactide, copolymers ofD,L-PLA and PGA, have particularly proven themselves according to theinvention.

For the objectives of the present invention especially the followingpolymers are particularly suited:

-   1) Poly-L-lactide (PLLA), preferably having inherent viscosity    within the range from 0.5 dl/g to 2.5 dl/g, favorably within the    range from 0.8 dl/g to 2.0 dl/g, especially within the range from    0.8 dl/g to 1.2 dl/g (each time measured 0.1% in chloroform at 25°    C.), preferably having a glass transition temperature ranging from    60° C. to 65° C., further preferred having a melting temperature    ranging from 180° C. to 185° C., moreover preferred    ester-terminated;-   2) Poly(D,L-lactide), preferably with inherent viscosity within the    range from 1.0 dl/g to 3.0 dl/g, favorably within the range from 1.5    dl/g to 2.5 dl/g, especially within the range from 1.8-2.2 dl/g    (each time measured 0.1% in chloroform at 25° C.), preferably having    a glass transition temperature ranging from 55° C. to 60° C.,    wherein the best results are obtained using a poly-L-lactide which    preferably has an inherent viscosity within the range from 0.5 dl/g    to 2.5 dl/g, favorably within the range from 0.8 dl/g to 2.0 dl/g,    especially within the range from 0.8 dl/g to 1.2 dl/g (each time    measured 0.1% in chloroform at 25° C.), preferably has a glass    transition temperature ranging from 60° C. to 65° C., further    preferred has a melting temperature ranging from 180° C. to 185° C.    and moreover is preferably ester-terminated.

Within the scope of the present invention, the small particles usablefor the production of said composite powder comprise at least onecalcium salt. Especially suited calcium salts comprise calciumphosphates, especially Ca₃(PO₄)₂, CaHPO₄, Ca(H₂PO₄)₂ and/orCa₅(PO₄)₃(OH), and calcium carbonate, especially precipitated calciumcarbonate particles. For the purpose of the present invention, calciumcarbonates have turned out to be particularly advantageous.

The form of the calcium salt, preferred of the calcium carbonate,especially of the precipitated calcium carbonate particles, is notsubject to any further restrictions and can be adapted to the concreteapplication. Of preference, scalenohedral, rhombohedral, needle-shaped,plate-shaped or ball-shaped (spherical) particles are used, however.

Within the scope of a very particularly preferred embodiment of thepresent invention, spherical precipitated calcium carbonate particlesare used, as they typically show an isotropic property profile.Accordingly, expediently the particles of the resulting composite powderequally excel by a preferably isotropic property profile.

In accordance with the invention, the term “calcium carbonate particles”also comprises fragments of particles which are obtainable e.g. bygrinding the calcium carbonate. The fraction of fragments, especially ofball fragments, is preferably less than 95%, preferred less than 75%,especially preferred less than 50%, especially less than 25%, eachrelated to the total quantity of preferably precipitated calciumcarbonate.

The aspect ratio (side ratio) of the calcium salt, preferred of thecalcium carbonate, especially of the precipitated calcium carbonateparticles, is preferably less than 5, of preference less than 4,especially preferred less than 3, favorably less than 2, even morepreferred less than 1.5, particularly preferred in the range from 1.0 to1.25, preferably less than 1.1, especially less than 1.05.

The aspect ratio (side ratio) of the calcium salt, preferred of thecalcium carbonate, especially of the precipitated calcium carbonateparticles, in this context denotes the quotient of maximum and minimumparticle diameters. It is preferably established by means ofelectron-microscopic images as means value (number average). In thiscontext, for spherical calcium carbonate particles preferably onlyparticles having a particle size in the range from 0.1 μm to 40.0 μm,especially in the range from 0.1 μm to 30.0 μm are considered. Forrhombohedral calcium salt particles, especially for rhombohedral calciumcarbonate particles, preferably only particles having a particle size inthe range from 0.1 μm to 30.0 μm, especially in the range from 0.1 μm to20.0 μm are considered. For other calcium salt particles, especially forcalcium carbonate particles, preferably only particles having a particlesize in the range from 0.1 μm to 2.0 μm are considered.

Moreover, preferably at least 90%, favorably at least 95% of allparticles have an aspect ratio (side ratio) of less than 5, preferablyless than 4, especially preferred less than 3, favorably less than 2,even more preferred less than 1.5, very particularly preferred rangingfrom 1.0 to 1.25, preferably less than 1.1, especially less than 1.05.

Further, spherical calcium carbonate particles are extraordinarilyappropriate.

In accordance with the invention, the calcium salt particles, especiallythe preferably spherical calcium carbonate particles, are expedientlyprovided predominantly in single parts. Further, minor deviations fromthe perfect particle shape, especially from the perfect ball shape, areaccepted as long as the properties of the particles are not basicallymodified. In this way, the surface of the particles may includeoccasional defects or additional depositions.

Within the scope of an especially preferred variant of the presentinvention, the calcium salt particles, preferred the calcium carbonateparticles, especially the precipitated calcium carbonate particles, arepreferably spherical and substantially amorphous. The term “amorphous”in this context refers to such calcium salt modifications in which theatoms at least partly do not form ordered structures but form anirregular pattern and therefore only have a short-range order but not along-range order. Herefrom crystalline modifications of the calciumsalt, such as e.g. calcite, vaterite and aragonite, in which the atomshave both a short-range order and a long-range order have to bedistinguished.

Within the scope of this preferred variant of the present invention, thepresence of crystalline parts is not categorically ruled out. Preferablythe fraction of crystalline calcium salts, especially of crystallinecalcium carbonate, is less than 50 wt.-%, especially preferred less than30 wt.-%, quite particularly preferred less than 15 wt.-%, especiallyless than 10 wt.-%, however. Within the scope of an especially preferredvariant of the present invention, the fraction of crystalline calciumsalts, especially of crystalline calcium carbonate, is less than 8.0wt.-%, preferably less than 6.0 wt.-%, appropriately less than 4.0wt.-%, especially preferred less than 2.0 wt.-%, quite particularlypreferred less than 1.0 wt.-%, especially less than 0.5 wt.-%, eachrelated to the total weight of the calcium salt.

For establishing the amorphous and the crystalline fractions, X-raydiffraction with an internal standard, preferably quartz, in combinationwith Rietveld refinement has particularly proven itself.

Within the scope of this preferred embodiment of the present invention,the calcium salt particles, preferred the preferably amorphous calciumcarbonate particles, are favorably stabilized by at least one substance,especially at least one surface-active substance, which is preferablyarranged on the surface of the calcium salt particles, especially on thesurface of the preferably spherical calcium carbonate particles.“Surface-active substances” in accordance with the present inventionexpediently denote organic compounds which strongly enrich themselvesfrom their solution at boundary surfaces (water/calcium salt particles,preferred calcium carbonate particles) and thus reduce the surfacetension, preferably measured at 25° C. For further details, reference ismade to technical literature, especially to Rompp-LexikonChemie/publisher Jurgen Falbe; Manfred Regitz. Revised by EckardAmelingmeier; Stuttgart, New York; Thieme; Volume 2: Cm-G; 10^(th)Edition (1997); keyword: “surface-active substances”.

Of preference, the substance, especially the surface-active substance,has a molar mass of more than 100 g/mol, preferably more than 125 g/mol,especially more than 150 g/mol, and satisfies the formula R—X_(n).

The remainder R stands for a remainder comprising at least 1, preferablyat least 2, of preference at least 4, especially preferred at least 6,especially at least 8, carbon atoms, preferably for an aliphatic orcycloaliphatic remainder which may comprise further remainders X, wherenecessary, and which may have one or more ether links, where necessary.

The remainder X stands for a group which comprises at least on oxygenatom as well as at least one carbon atom, sulfur atom, phosphorus atomand/or nitrogen atom, preferred at least one phosphorus atom and/or atleast one carbon atom. Especially preferred are the following groups:

-   -   carboxylic acid groups —COON,    -   carboxylate groups ˜COO⁻,    -   sulfonic groups ˜SO₃H,    -   sulfonate groups ˜SO₃ ⁻,    -   hydrogen sulfate groups ˜OSO₃H,    -   sulfate groups ˜OSO₃ ⁻,    -   phosphonic acid groups ˜PO₃H₂,    -   phosphonate groups ˜PO₃H⁻, ˜PO₃ ²⁻,    -   amino groups ˜NR¹R² as well as    -   ammonium groups ˜N⁺R¹R²R³,        especially carboxylic acid groups, carboxylate groups,        phosphonic acid groups and phosphonate groups.

The remainders R¹, R² and R³ in this context stand independently of eachother for hydrogen or an alkyl group having 1 to 5 carbon atoms. One ofthe remainders R¹, R² and R³ may also be a remainder R.

Preferred counter-ions for the afore-mentioned anions are metal cations,especially alkaline metal cations, preferred Na⁺ and K⁺, as well asammonium ions.

Preferred counter-ions for the afore-mentioned cations are hydroxy ions,hydrogen carbonate ions, carbonate ions, hydrogen sulfate ions, sulfateions and halide ions, especially chloride and bromide ions.

n stands for a preferably integer within the range from 1 to 20,preferred within the range from 1 to 10, especially within the rangefrom 1 to 5.

Substances especially suited for the purposes of the present inventioncomprise alkyl carboxylic acids, alkyl carboxylates, alkyl sulfonicacids, alkyl sulfonates, alkyl sulfates, alkyl ether sulfates havingpreferably 1 to 4 ethylene glycol ether units, fatty alcohol ethoxylatehaving preferably 2 to 20 ethylene glycol ether units, alkyl phenolethoxylate, possibly substituted alkyl phosphonic acids, possiblysubstituted alkyl phosphonates, sorbitan fatty acid esters, alkyl polyglucosides, N-methyl glucamides, homopolymers and copolymers of theacrylic acid and the corresponding salt forms and block copolymersthereof.

A first group of especially advantageous substances are possiblysubstituted alkyl phosphonic acids, especially amino-tri-(methylenephosphonic acid), 1-hydroxy ethylene-(1,1-diphosphonic acid), ethylenediamine-tetra-(methylene phosphonic acid), hexamethylenediamine-tetra-(methylene phosphonic acid), diethylenetriamine-penta-(methylene phosphonic acid), as well as possiblysubstituted alkyl phosphonates, especially of the afore-mentioned acids.Said compounds are known as multifunctional sequestration means formetal ions and stone inhibitors.

Furthermore, also homopolymers and copolymers, preferably homopolymers,of the acrylic acid as well as the corresponding salt forms thereof haveespecially proven themselves, in particular those having a weightaverage molecular weight within the range from 1,000 g/to 10,000 g/mol.

Further, the use of block copolymers, preferably of double-hydrophilicblock copolymers, especially of polyethylene oxide or polypropyleneoxide, is especially appropriate.

The fraction of the preferably surface-active substances may basicallybe freely selected and specifically adjusted for the respectiveapplication. However, it is preferred to be within the range from 0.1wt.-% to 5.0 wt.-%, especially within the range from 0.3 wt.-% to 1.0wt.-%, based on the calcium salt content, especially the CaCO₃ content,of the particles.

The preferably spherical, preferably amorphous calcium salt particles,especially the calcium carbonate particles, may be prepared in a wayknown per se, e.g. by hydrolysis of dialkyl carbonate or of alkylenecarbonate in a solution comprising calcium cations.

The preparation of non-stabilized spherical calcium carbonate particlesis described in detail e.g. in the patent application WO 2008/122358 thedisclosure of which, especially relating to especially expedientvariants of the preparation of said non-stabilized spherical calciumcarbonate particles, is explicitly incorporated here by reference.

The hydrolysis of the dialkyl carbonate or the alkylene carbonate isusefully carried out in the presence of a hydroxide.

Substances preferred for the purpose of the present invention whichcontain Ca²⁺ ions are calcium halides, preferably CaCl₂, CaBr₂,especially CaCl₂, as well as calcium hydroxide. Within the scope of thefirst especially preferred embodiment of the present invention CaCl₂ isused. In a further especially preferred embodiment of the presentinvention Ca(OH)₂ is used.

Within the scope of a first especially preferred embodiment of thepresent invention, a dialkyl carbonate is used. Particularly suiteddialkyl carbonates comprise 3 to 20, preferably 3 to 9, carbon atoms,especially dimethyl carbonate, diethyl carbonate, di-n-propyl carbonate,di-iso-propyl carbonate, di-n-butyl carbonate, di-sec-butyl carbonateand di-tert-butyl carbonate, with dimethyl carbonate beingextraordinarily preferred in this context.

In another especially preferred embodiment of the present invention, analkylene carbonate is reacted. Especially expedient alkylene carbonatescomprise 3 to 20, preferred 3 to 9, especially preferred 3 to 6, carbonatoms and include especially those compounds containing a ring of 3 to8, preferred 4 to 6, especially 5, atoms having preferably 2 oxygenatoms and otherwise carbon atoms. Propylene carbonate(4-methyl-1,3-dioxolane) has especially proven itself in this context.

Alkaline metal hydroxides, especially NaOH and calcium hydroxide, haveturned out to be especially suited hydroxides. Within the scope of afirst especially preferred embodiment of the present invention, NaOH isused. Within the scope of another especially preferred embodiment of thepresent invention Ca(OH)₂ is used.

Further, the molar ratio of Ca²⁺, preferably of calcium chloride, toOH⁻, preferably alkali metal hydroxide, in the reaction mixture ispreferably higher than 0.5:1 and especially preferred within the rangeof >0.5:1 to 1:1, especially within the range from 0.6:1 to 0.9:1.

The molar ratio of Ca²⁺, preferably of calcium chloride, to dialkylcarbonate and/or alkylene carbonate in the reaction mixture favorably iswithin the range from 0.9:1.5 to 1.1:1, especially preferred within therange from 0.95:1 to 1:0.95. Within the scope of a particularlyexpedient variant of the present invention, dialkyl carbonate and/oralkylene carbonate and Ca²⁺, especially calcium chloride, are used to beequimolar.

Within a first particularly preferred variant of the present invention,it is not Ca(OH)₂ which is used as OH⁻ source. The components for thereaction are favorably used in the following concentrations:

-   -   a) Ca²⁺: >10 mmol/l to 50 mmol/l, preferably 15 mmol/l to 45        mmol/l, especially 17 mmol/l to 35 mmol/l;    -   b) dialkyl carbonate and/or    -   alkylene carbonate: >10 mmol/l to 50 mmol/l, preferably 15        mmol/l to 45 mmol/l, especially 17 mmol/l to 35 mmol/l;    -   c) OH⁻: 20 mmol/l to 100 mmol/l, preferably 20 mmol/l to 50        mmol/l, especially preferred 25 mmol/l to 45 mmol/l, especially        28 mmol/l to 35 mmol/l.

The respective indicated concentrations relate to the concentrations ofthe given components in the reaction mixture.

Within a further especially preferred variant of the present invention,Ca(OH)₂, preferred limewater, especially saturated limewater, is used asOH⁻ source. The components for the reaction are favorably used in thefollowing concentrations:

-   -   a) Ca(OH)₂: >5 mmol/l to 25 mmol/l, preferred 7.5 mmol/l to 22.5        mmol/l, especially 8.5 mmol/l to 15.5 mmol/l;    -   b) dialkyl carbonate and/or        -   alkylene carbonate: >5 mmol/l to 25 mmol/l, preferred 7.5            mmol/l to 22.5 mmol/l, especially 8.5 mmol/l to 15.5 mmol/l.

The respective indicated concentrations relate to the concentrations ofsaid components in the reaction mixture.

The reaction of the components is preferably carried out at atemperature within the range from 15° C. to 30° C.

The concrete size of the calcium salt particles, especially the calciumcarbonate particles, can be controlled via oversaturation in a mannerknown per se.

The calcium salt particles, especially the calcium carbonate particles,precipitate from the reaction mixture under the afore-mentionedconditions.

The preferably amorphous calcium salt particles, especially thepreferably amorphous calcium carbonate particles, are expedientlystabilized by addition of the preferably surface-active substance to thereaction mixture.

Said addition of the substance should not take place before the start ofreaction to form the calcium salt particles, especially the calciumcarbonate particles, i.e. not before addition of the educts, preferablyno earlier than 1 minute, preferably no earlier than 2 minutes,appropriately no earlier than 3 minutes, especially preferred no earlierthan 4 minutes, especially no earlier than 5 minutes, after mixing theeducts. Further, the point in time of the addition should be selected sothat the preferably surface-active substance is added shortly before theend of precipitation and as shortly as possible before the start ofconversion of the preferably amorphous calcium salt, especially theamorphous calcium carbonate, to a crystalline modification, as in thisway the yield and the purity of the “stabilized spherical amorphouscalcium salt particles” can be maximized. If the preferablysurface-active substance is added earlier, usually a bimodal product isobtained which comprises, apart from the desired stabilized sphericalamorphous calcium salt particles, ultra-fine amorphous calcium saltparticles as a side-product. If the preferably surface-active substanceis added later, then the conversion of the desired “stabilized calciumsalt particles” to crystalline modifications already starts.

For this reason, the preferably surface-active substance is preferablyadded at a pH value less than or equal to 11.5, preferably less than orequal to 11.3, especially less than or equal to 11.0. Especiallyfavorable is an addition at a pH value in the range from 11.5 to 10.0,of preference in the range from 11.3 to 10.5, especially in the rangefrom 11.0 to 10.8, each measured at the reaction temperature, preferablyat 25° C.

The resulting stabilized preferably spherical amorphous calcium saltparticles can be dehydrated and dried in a way known per se, e.g. bycentrifugation. Washing with acetone and/or drying in the vacuum dryingcabinet is no longer absolutely necessary.

By drying “calcium salt particles having low structural water content”,especially “calcium carbonate particles having low structural watercontent” are obtainable from the “stabilized calcium salt particles”.

For the purposes of the present invention, the calcium salt particlesobtained are preferably dried such that they have the desired residualwater content. For this, a procedure in which the calcium salt particlesare pre-dried preferably at first at a temperature up to 150° C. andsubsequently the calcium salt particles are dried preferably at atemperature ranging from more than 150° C. to 250° C., preferred rangingfrom 170° C. to 230° C., especially preferred ranging from 180° C. to220° C., especially ranging from 190° C. to 210° C. Drying is preferablycarried out in the circulating air drying cabinet. Accordingly, thecalcium salt particles are expediently dried for at least 3 h,especially preferred for at least 6 h, especially for at least 20 h.

Within the scope of another especially preferred variant of the presentinvention, the calcium salt particles, especially the preferablyprecipitated calcium carbonate particles, are substantially crystalline,especially substantially calcitic. Within the scope of this preferredvariant of the present invention, the presence of other, especially ofamorphous parts is not categorically excluded. Preferably the fractionof other non-crystalline calcium salt modifications, especially ofnon-crystalline calcium carbonate modifications, is less than 50 wt.-%,especially preferred less than 30 wt.-%, particularly preferred lessthan 15 wt.-%, especially less than 10 wt.-%, however. Moreover, thefraction of non-calcitic calcium carbonate modifications preferably isless than 50 wt.-%, especially preferred less than 30 wt.-%,particularly preferred less than 15 wt.-%, especially less than 10wt.-%.

For establishing the amorphous and crystalline fractions, the X-raydiffraction with an internal standard, preferably aluminum oxide, incombination with Rietveld refinement has particularly proven itself.

The mean diameter of the small particles is within the range from 0.01μm to 1.0 mm, preferred within the range from 0.05 μm to 50.0 μm,especially within the range from 2.5 μm to 30.0 μm.

Within the scope of an especially preferred embodiment of the presentinvention, the mean diameter of the small particles is more than 3.0 μm,preferably more than 4.0 μm, expediently more than 5.0 μm, expedientlymore than 6.0 μm, preferred more than 7.0 μm, especially preferred morethan 8.0 μm, yet more preferred more than 9.0 μm, particularly preferredmore than 10.0 μm, yet more preferred more than 11.0 μm, above all morethan 12.0 μm, especially more than 13.0 μm.

For small particles comprising scalenohedral calcium salt particles,especially scalenohedral calcium carbonate particles, the mean diameterof the small particles favorably is within the range from 0.05 μm to 5.0μm, preferred within the range from 0.05 μm to 2.0 μm, preferably lessthan 1.75 μm, especially preferred less than 1.5 μm, especially lessthan 1.2 μm. Furthermore, the mean particle diameter in this case isfavorably more than 0.1 μm, preferably more than 0.2 μm, especially morethan 0.3 μm.

Furthermore, also small particles comprising scalenohedral calcium saltparticles, especially scalenohedral calcium carbonate particles, havinga mean diameter of the small particles favorably within the range from1.0 μm to 5.0 μm, preferably less than 4.5 μm, especially preferred lessthan 4.0 μm, especially less than 3.5 μm, have particularly proventhemselves. Furthermore, the mean particle diameter in this case isfavorably more than 1.5 μm, preferably more than 2.0 μm, especially morethan 3.0 μm.

For small particles comprising rhombohedral calcium salt particles,especially rhombohedral calcium carbonate particles, the mean diameterof the small particles favorably is within the range from 0.05 μm to30.0 μm, preferred within the range from 0.05 μm to 2.0 μm, preferablyless than 1.75 μm, especially preferred less than 1.5 μm, especiallyless than 1.2 μm. Furthermore, the mean particle diameter in this caseis favorably more than 0.1 μm, preferably more than 0.2 μm, especiallymore than 0.3 μm.

Furthermore, also small particles comprising rhombohedral calcium saltparticles, especially rhombohedral calcium carbonate particles, having amean diameter favorably within the range from 1.0 μm to 30.0 μm,preferred within the range from 1.0 μm to 20.0 μm, preferably less than18.0 μm, especially preferred less than 16.0 μm, especially less than14.0 μm, have particularly proven themselves. Furthermore, in this casethe mean particle diameter is favorably more than 2.5 μm, preferablymore than 4.0 μm, especially more than 6.0 μm.

For small particles comprising needle-shaped calcium salt particles,especially needle-shaped calcium carbonate particles, the mean diameterof the small particles is favorably within the range from 0.05 μm to 2.0μm, preferably less than 1.5 μm, especially preferred less than 1.0 μm,especially less than 0.75 μm. Furthermore, the mean particle diameter inthis case is favorably more than 0.1 μm, preferably more than 0.2 μm,especially more than 0.3 μm.

For small particles comprising needle-shaped calcium salt particles,especially needle-shaped calcium carbonate particles, the aspect ratioof the particles is preferably more than 2, preferred more than 5,especially preferred more than 10, especially more than 20. Furthermore,the length of the needles preferably is within the range from 0.1 μm to100.0 μm, preferred within the range from 0.3 μm to 85.0 μm, especiallywithin the range from 0.5 μm to 70.0 μm.

For small particles comprising plate-shaped calcium salt particles,especially plate-shaped calcium carbonate particles, the mean diameterof the small particles is favorably within the range from 0.05 μm to 2.0μm, preferably less than 1.75 μm, especially preferred less than 1.5 μm,especially less than 1.2 μm. Furthermore, the mean particle diameter inthis case is favorably more than 0.1 μm, preferably more than 0.2 μm,especially more than 0.3 μm.

For small particles comprising spherulitic (spherical) calcium carbonateparticles the mean diameter of the small particles expediently is morethan 2.5 μm, favorably more than 3.0 μm, preferred more than 4.0 μm,especially preferred more than 5.0 μm, especially more than 6.0 μm.Furthermore, the mean particle diameter is expediently less than 30.0μm, favorably less than 20.0 μm, preferred less than 18.0 μm, especiallypreferred less than 16.0 μm, especially less than 14.0 μm.

The afore-mentioned mean particles sizes of the small particles areestablished, within the scope of the present invention, expediently byevaluation of scanning electron microscope images (SEM images), whereinpreferably only particles having a minimum size of 0.01 μm areconsidered and a number average is formed over preferably at least 20,especially preferred at least 40 particles. Furthermore, alsosedimentation analysis methods have especially proven themselves,primarily for small particles comprising needle-shaped calcium saltparticles, especially needle-shaped calcium carbonate particles, whereinin this context the use of a Sedigraph 5100 (Micromeritics GmbH) is ofparticular advantage.

In the case of small particles comprising non-spherical calcium saltparticles, especially non-spherical calcium carbonate particles,preferably the ball-equivalent particle size is focused.

The size distribution of the small particles comprising calcium saltparticles, especially calcium carbonate particles, is comparativelynarrow and preferably such that at least 90.0 wt.-% of all smallparticles have a particle diameter within the range from mean particlediameter −50%, preferably within the range from mean particle diameter−40%, especially within the range from mean particle diameter −30%, tomean particle diameter+70%, preferably mean particle diameter+60%,especially mean particle diameter+50%. Accordingly, the sizedistribution is preferably established by means of scanning tunnelingmicroscopy.

The form factor of the small particles, currently defined as thequotient of minimum particle diameter and maximum particle diameter,expediently is more than 0.90, especially preferred more than 0.95expediently for at least 90%, favorably for at least 95% of allparticles. In this context, for small particles comprising sphericalcalcium carbonate particles preferably only particles having a particlesize within the range from 0.1 μm to 30.0 μm are considered. For smallparticles comprising rhombohedral calcium salt particles, especiallyrhombohedral calcium carbonate particles, preferably only particleshaving a particle size within the range from 0.1 μm to 20.0 μm areconsidered. For small particles comprising other calcium salt particles,especially other calcium carbonate particles, preferably only particleshaving a particle size within the range from 0.1 μm to 2.0 μm areconsidered.

The calcium salt particles, especially the calcium carbonate particles,favorably further excel by a comparatively low water content. Theyexpediently have a water content (residual moisture at 200° C.), basedon their total weight, not exceeding 5.0 wt.-%, preferably not exceeding2.5 wt.-%, preferably not exceeding 1.0 wt.-%, especially preferred notexceeding 0.5 wt.-%, yet more preferred less than 0.4 wt.-%, expedientlyless than 0.3 wt.-%, favorably less than 0.2 wt.-%, especially withinthe range from >0.1 wt.-% to <0.2 wt.-%.

Within the present invention, the water content of the calcium saltparticles, especially of the calcium carbonate particles, is establishedpreferably by means of thermal gravimetry or by means of a rapidinfrared drier, e.g. MA35 or MA45 by Sartorius or halogen moistureanalyzer HB43 by Mettler, wherein the measurement is preferably carriedout under nitrogen (nitrogen flow rate of preferably 20 ml/min) andexpediently via the temperature range of 40° C. or less to 250° C. ormore. Further, the measurement is preferably carried out at a heatingrate of 10° C./min.

The specific surface of the calcium salt particles, especially thecalcium carbonate particles, is preferably within the range from 0.1m²/g to 100 m²/g, especially preferred within the range from 0.1 m²/g to20.0 m²/g, especially within the range from 4.0 m²/g to 12.0 m²/g. Forrhombohedral calcium salt particles, especially for rhombohedral calciumcarbonate particles, the specific surface within the scope of anespecially preferred variant of the present invention is less than 1.0m²/g, preferred less than 0.75 m²/g, especially less than 0.5 m²/g,wherein the mean diameter of the rhombohedral calcium salt particles,especially the rhombohedral calcium carbonate particles, is favorablymore than 2.5 μm, preferably more than 4.0 μm, especially more than 6.0μm.

For spherical calcium carbonate particles, the specific surface withinthe scope of an especially preferred variant of the present invention isless than 3.0 m²/g, preferred less than 2.0 m²/g, especially less than1.5 m²/g. Furthermore, the specific surface in this case favorably ismore than 0.25 m²/g, preferably more than 0.5 m²/g, especially more than0.75 m²/g.

Particularly preferred in this context are calcium salt particles,especially calcium carbonate particles, the specific surface of whichremains relatively constant during drying and preferably varies by nomore than 200%, preferred by no more than 150%, especially by no morethan 100%, each related to the initial value.

The basicity of the calcium salt particles, especially the calciumcarbonate particles, is comparatively low. Its pH value, measuredaccording to EN ISO 787-9, is preferably less than 11.5, preferred lessthan 11.0, especially less than 10.5.

The preferably spherical calcium carbonate particles may be prepared bycarbonizing an aqueous calcium hydroxide (Ca(OH)₂) suspension. For this,expediently CO₂ or a CO₂-containing gas mixture is fed into a calciumhydroxide suspension.

A procedure in which

-   a. an aqueous calcium hydroxide suspension is provided,-   b. into the suspension of step a. carbon dioxide or a gas mixture    containing carbon dioxide is introduced and-   c. the forming calcium carbonate particles are separated,    has especially proven itself, wherein further 0.3 wt.-% to 0.7    wt.-%, preferably 0.4 wt.-% to 0.6 wt.-%, especially 0.45 wt.-% to    0.55 wt.-%, of at least one amino tri alkylene phosphonic acid are    added.

The concentration of the calcium hydroxide suspension is not subject toany particular restrictions. However, a concentration within the rangefrom 1 g CaO/I to 100 g CaO/I, preferred within the range from 10 gCaO/I to 90 g CaO/I, especially within the range from 50 g CaO/I to 80 gCaO/I is especially favorable.

As amino tri alkylene phosphonic acid, preferably amino tri methylenephosphonic acid, amino tri ethylene phosphonic acid, amino tri propylenephosphonic acid and/or amino tri butylene phosphonic acid, especiallyamino tri methylene phosphonic acid is/are added.

The conversion of the reaction can be controlled by the quantity of CO₂introduced. However, the introduction of carbon dioxide or the carbondioxide-containing gas mixture is preferably carried out until thereaction mixture has a pH value of less than 9, preferably less than 8,especially less than 7.5.

Furthermore, the carbon dioxide or the carbon dioxide-containing gasmixture is expediently introduced at a gas flow rate within the rangefrom 0.02 l CO₂/(h*g Ca(OH)₂) to 2.0 l CO₂/(h*g Ca(OH)₂), preferablywithin the range from 0.04 l CO₂/(h*g Ca(OH)₂) to 1.0 l CO₂/(h*gCa(OH)₂), especially preferred within the range from 0.08 l CO₂/(h*gCa(OH)₂) to 0.4 l CO₂/(h*g Ca(OH)₂), especially within the range from0.12 l CO₂/(h*g Ca(OH)₂) to 0.2 l CO₂/(h*g Ca(OH)₂) into the calciumhydroxide suspension.

Incidentally, the conversion of the calcium hydroxide suspension withthe carbon dioxide or the carbon dioxide-containing gas mixture iscarried out preferably at a temperature of less than 25° C., preferablyless than 20° C., especially less than 15° C. On the other hand, thereaction temperature preferably is more than 0° C., preferably more than5° C., especially more than 7° C.

The at least one amino tri alkylene phosphonic acid is expediently addedin the course of the reaction, preferably after an abrupt drop of theconductance of the reaction mixture. Expediently, the at least one aminotri alkylene phosphonic acid is added as soon as the conductivity of thereaction mixture decreases by more than 0.5 mS/cm/min. The decrease ofthe conductivity of the reaction mixture preferably amounts to at least0.25 mS/cm within 30 seconds, especially at least 0.5 mS/cm within 60seconds. Within the scope of an especially preferred embodiment of thepresent invention, the at least one amino tri alkylene phosphonic acidis added at the end of precipitation of the basic calcium carbonate(BCC; 2CaCO₃*Ca(OH)₂*nH₂O).

The calcium carbonate particles precipitate from the reaction mixtureunder the afore-mentioned conditions and can be separated and dried in away known per se.

Within the scope of a preferred embodiment of the present invention, thecomposite powder according to the invention used in the implant containsa mixture comprising calcium carbonate and further calcium salts,especially calcium phosphates, especially Ca₃(PO₄)₂, CaHPO₄, Ca(H₂PO₄)₂and/or Ca₅(PO₄)₃(OH). The weight ratio of calcium carbonate to calciumphosphate preferably is in the range from 99:1 to 1:99, especially inthe range from 50:50 to 99:1.

Within the scope of a preferred embodiment, the small particles compriseinhibiting calcium carbonate particles. In this context, “inhibitingcalcium carbonate particles” denote calcium carbonate particles which asan additive in polymers decelerate, at the best completely suppress, theacid-catalyzed degradation of the polymer as compared to the samepolymer without an additive.

Expediently, the small particles are obtainable by a process in whichcalcium carbonate particles are coated with a composition whichcontains, each related to its total weight, a mixture of at least 0.1wt.-% of at least one calcium complexing agent and/or at least oneconjugated base which is an alkali metal salt or calcium salt of a weakacid, together with at least 0.1 wt.-% of at least one weak acid.

The anions of the calcium complexing agent and of the conjugated basemay be equal, within the scope of this embodiment, although this is noabsolute requirement.

Sodium phosphates, i.e. sodium salts of phosphoric acids, especiallysodium salts of orthophosphoric acid, metaphosphoric acid andpolyphosphoric acid, have turned out to be especially advantageous ascalcium complexing agents. Preferred sodium phosphates comprise sodiumorthophosphates such as primary sodium dihydrogen phosphate NaH₂PO₄,secondary sodium dihydrogen phosphate Na₂HPO₄ and tertiary trisodiumphosphate Na₃PO₄; sodium iso polyphosphates such as tetrasodiumdiphosphate (sodium pyrophosphate) Na₄P₂O₇, pentasodium triphosphate(sodium tripolyphosphate) Na₅P₃O₁₀; as well as higher-molecular sodiumphosphates such as sodium metaphosphates and sodium polyphosphates suchas fused or thermal phosphates, Graham's salt (approximate compositionNa₂O*P₂O₅, occasionally also referred to as sodium hexametaphosphate),Kurrol's salt and Maddrell salt. Especially preferred, sodiumhexametaphosphate is used according to the invention. The use of theafore-mentioned phosphates is especially advantageous in a compositepowder for implants, as in this case the phosphates additionally promotethe osseous structure.

Further suited calcium complexing agents include joint multidentatechelate-forming ligands, especially ethylene diamino tetra acetic acid(EDTA), triethylenetetramine, diethylenetriamine, o-phenanthroline,oxalic acid and mixtures thereof.

Weak acids especially suited for the purposes of the present inventionhave a pKa value, measured at 25° C., of more than 1.0, preferably morethan 1.5, especially more than 2.0. At the same time, the pKa value ofsuited weak acids, measured at 25° C., is preferably less than 20.0,preferred less than 10.0, especially preferred less than 5.0,expediently less than 4.0, especially less than 3.0. Weak acidsextraordinarily suited according to the invention comprise phosphoricacid, metaphosphoric acid, hexametaphosphoric acid, citric acid, boricacid, sulfurous acid, acetic acid and mixtures thereof. Phosphoric acidis used especially preferred as weak acid.

Conjugated bases preferred according to the invention include especiallysodium salts or calcium salts of the afore-mentioned weak acids, withsodium hexametaphosphate being particularly preferred.

The inhibiting calcium carbonate particles can be prepared in a wayknown per se by coating calcium carbonate particles with a compositionwhich comprises at least one calcium complexing agent and/or at leastone conjugated base which is an alkali metal salt or calcium salt of aweak acid, together with at least one weak acid.

Expediently an aqueous suspension of the calcium carbonate particles tobe coated is provided which, based on its total weight, favorably has acontent of calcium carbonate particles within the range from 1.0 wt.-%to 80.0 wt.-%, preferred within the range from 5.0 wt.-% to 50.0 wt.-%,especially within the range from 10.0 wt.-% to 25.0 wt.-%.

The coating of the calcium carbonate particles is favorably carried outby adding said substances in pure form or in aqueous solution, whereinaqueous solutions of said components have turned out to be particularlyadvantageous according to the invention in order to obtain an ashomogenous coating as possible of the calcium carbonate particles.

Further, it is especially favorable within the scope of the presentinvention to add the calcium complexing agent and/or the conjugatedbase, which is an alkali metal salt or calcium salt of a weak acid,before the weak acid.

The calcium complexing agent or the conjugated base is preferably usedin a quantity ranging from 0.1 parts by weight to 25.0 parts by weight,preferred ranging from 0.5 parts by weight to 10.0 parts by weight,especially ranging from 1.0 parts by weight to 5.0 parts by weight, eachrelated to 100 parts by weight of the calcium carbonate particles to becoated. The quantity of the calcium complexing agent or of theconjugated base is expediently selected so that complete coating of thesurface of the calcium carbonate particles with the calcium complexingagent of the conjugated base is obtained.

The weak acid is preferably used in a quantity ranging from 0.1 parts byweight to 30.0 parts by weight, preferred ranging from 0.5 parts byweight to 15.0 parts by weight, especially preferred ranging from 1.0parts by weight to 10.0 parts by weight, especially ranging from 4.0parts by weight to 8.0 parts by weight, each related to 100 parts byweight of the calcium carbonate particles to be coated.

The inhibiting calcium carbonate particles obtainable in this way arestable in a moderately acid environment, wherein this capacity is due toa buffering action by the absorbed or converted calcium complexing agentor the conjugated base on the surface of the calcium carbonate particlesand the weak acid in solution, wherein applying the calcium complexingagent and/or the conjugated base to the surface of the calcium carbonateparticles in turn reduces the solubility of the surface of the calciumcarbonate particles and thus stabilizes the calcium carbonate particleswithout the teaching of the present invention being intended to be boundto this theory.

The said composite powder is preferably obtainable by a method in whichlarge particles are combined with small particles, wherein

-   -   the large particles have a mean particle ranging from 10 μm to        10 mm, favorably ranging from 20 μm to 10 mm, especially        preferred ranging from 30 μm to 2.0 mm, especially ranging from        60.0 μm to 500.0 μm,    -   the mean particle diameter of the small particles preferably is        no more than ⅕, preferred no more than 1/10, especially        preferred no more than 1/20, especially no more than 1/1000, of        the mean particle diameter of the large particles.

The small particles preferably are arranged on the surface of the largeparticles and/or are non-homogeneously spread within the largeparticles.

Especially for absorbable polymers and for UHMWPE excellent results areachieved, however, when the small particles are arranged on the surfaceof the large particles and preferably do not completely cover thelatter.

“Non-homogeneous” distribution of the small particles or fragmentsthereof within the large particles in this case means a non-homogeneous(uniform) distribution of the small particles or fragments thereofwithin the large particles. Preferably, within the particles of thecomposite powder there is at least a first area comprising at least two,preferably at least three, preferred at least four, especially at leastfive small particles or fragments thereof and at least another areawithin the particles of the composite powder which, although taking thesame volume and the same shape as the first area, comprises a differentnumber of small particles.

Within the scope of a preferred embodiment of the present invention, theweight ratio of polymer, especially polyamide, to calcium salt,preferred to calcium carbonate, especially to precipitated calciumcarbonate, within the particle interior is higher than the weight ratioof polymer, especially polyamide, to calcium salt, preferred to calciumcarbonate, especially precipitated calcium carbonate, in the outer areaof the particles. Expediently, the weight ratio of polymer, especiallypolyamide, to calcium salt, preferred to calcium carbonate, especiallyprecipitated calcium carbonate, in the particle interior is higher than50:50, preferred higher than 60:40, favorably higher than 70:30,especially preferred higher than 80:20, even more preferred higher than90:10, particularly preferred higher than 95:5, especially higher than99:1.

Furthermore, the weight ratio of calcium salt, preferred calciumcarbonate, especially precipitated calcium carbonate, to polymer,especially polyamide, in the outer area of the particles, preferably inthe preferred outer area of the particles, is higher than 50:50,preferred higher than 60:40, favorably higher than 70:30, especiallypreferred higher than 80:20, even more preferred higher than 90:10,particularly preferred higher than 95:5, especially higher than 99:1.

Within the scope of another preferred embodiment of the presentinvention, the small particles are arranged on the surface of the largeparticles and preferably do not completely cover the large particles.Expediently, at least 0.1%, preferred at least 5.0%, especially 50.0%,of the surface of the large particles are not coated with the calciumsalt particles, especially not coated with the preferably sphericalcalcium carbonate particles. This effect is preferably intensified bythe gaps between individual calcium salt particles, especially betweenindividual calcium carbonate particles which are preferably formed andresult in the formation of appropriate micro-channels for fluidsubstances, especially for a melt of the polymer of the large particles.Said structure is especially beneficial to applications of the compositepowder in laser sintering methods, as in this way uniform and rapidmelting of the polymer contained in the composite powder, preferred ofthe thermoplastic polymer, especially preferred of the absorbablepolymer, especially of the lactic acid polymer, is ensured.

The said composite powder is characterized by a specific particle sizedistribution. On the one hand, the particles of the composite powderpreferably have a mean particle size d₅₀ ranging from 10 μm to less than200 μm, preferred from 20 μm to less than 200 μm, especially preferredfrom 20 μm to less than 150 μm, favorably from 20 μm to less than 100μm, especially from 35 μm to less than 70 μm.

Furthermore, the fine fraction of the composite powder preferably isless than 50.0 vol %, preferred less than 45.0 vol %, especiallypreferred less than 40.0 vol %, even more preferred less than 20.0 vol%, favorably less than 15.0 vol %, expediently less than 10.0 vol %,especially less than 5.0 vol %. The fine fraction denotes, according tothe invention, the fraction of the smallest particle population in abimodal or multimodal grain size distribution related to the totalamount in the cumulative distribution curve. In unimodal (monodisperse)grain size distribution, the fine fraction is defined as 0.0 vol %,according to the invention. In this context, all particles present inthe product including non-bonded starting material, especially smallparticles in accordance with the invention as well as fragments of thelarge and/or small particles in accordance with the invention areconsidered.

For composite powders having an average particle size d₅₀ ranging frommore than 40 μm to less than 200 μm, the fine fraction preferably issuch that the fraction of particles within the product having a particlesize of less than 20 μm is preferably less than 50.0 vol %, preferredless than 45.0 vol %, especially preferred less than 40.0 vol %, evenmore preferred less than 20.0 vol %, favorably less than 15.0 vol %,expediently less than 10.0 vol %, especially less than 5.0 vol %,wherein “particles” in this context comprise especially particles of thecomposite powder in accordance with the invention, small particles inaccordance with the invention as well as fragments of the large and/orsmall particles in accordance with the invention, if they show the saidparticle size.

For composite powders having a mean particle size d₅₀ ranging from 10 μmto 40 μm, the fine fraction preferably is such that the fraction ofparticles within the product having a particle size of less than 5 μm ispreferably less than 50.0 vol %, preferred less than 45.0 vol %,especially preferred less than 40.0 vol %, even more preferred less than20.0 vol %, favorably less than 15.0 vol %, expediently less than 10.0vol %, especially less than 5.0 vol %, wherein “particles” in thiscontext comprise especially particles of the composite powder inaccordance with the invention, small particles in accordance with theinvention as well as fragments of the large and/or small particles inaccordance with the invention, if they show the said particle size.

Furthermore, the density of the fine fraction preferably is less than2.6 g/cm³, preferred less than 2.5 g/cm³, especially preferred less than2.4 g/cm³, especially ranging from more than 1.2 g/cm³ to less than 2.4g/cm³, said value being preferably determined by separating the finefraction by means of sieving and densitometry at the separated fraction.

Of preference, the particles of the composite powder have a particlesize d₉₀ of less than 350 μm, preferably less than 300 μm, preferredless than 250 μm, especially preferred less than 200 μm, especially lessthan 150 μm. Further, the particle size d₉₀ preferably is more than 50μm, preferred more than 75 μm, especially more than 100 μm.

Appropriately, the d₂₀/d₅₀ ratio is less than 100%, preferably less than75%, preferred less than 65%, especially preferred less than 60%,especially less than 55%. Further, the d₂₀/d₅₀ ratio appropriately ismore than 10%, preferably more than 20%, preferred more than 30%,especially preferred more than 40%, especially more than 50%.

The afore-mentioned variables d₂₀, d₅₀ and d₉₀ are defined as followswithin the scope of the present invention:

d₂₀ denotes the particle size of the particle size distribution at which20% of the particles have a particle size of less than the given valueand 80% of the particles have a particle size of more than or equal tothe given value.

d₅₀ denotes the mean particle size of the particle size distribution.50% of the particles have a particle size of less than the given valueand 50% of the particles have a particle size of more than or equal tothe given value.

d₉₀ denotes the particle size of the particle size distribution at which90% of the particles have a particle size of less than the given valueand 10% of the particles have a particle size of more than or equal tothe given value.

The particle size distribution according to the invention can beobtained in a way known per se by sizing the composite powder, i.e. byseparating a disperse solid mixture into fractions. Preferably, sizingis carried out according to particle size or particle density.Especially advantageous are dry sieving, wet sieving and air jetsieving, especially air jet sieving, as well as flow sizing, especiallyby means of air separation.

Within an especially preferred embodiment of the present invention, thecomposite powder is sized in a first step to preferably remove thecoarse fraction of more than 800 μm, preferred of more than 500 μm,especially of more than 250 μm. In this context, dry sieving via acoarse sieve which preferably has a size, i.e. the size of the holes,ranging from 250 μm to 800 μm, preferred ranging from 250 μm to 500 μm,especially of 250 mm, has especially stood the test.

In a further step, the composite powder is preferably sized topreferably remove the fine fraction of <20 μm. In this context, air jetsieving and air separation have turned out to be especially appropriate.

The mean diameters of the particles of the composite powder, the largeparticles and the small particles, the particle sizes d₂₀, d₅₀, d₉₀ aswell as the afore-mentioned lengths are established, according to theinvention, appropriately by way of microscopic images, by way ofelectron-microscopic images, where necessary. For establishing the meandiameters of the large particles and the small particles as well as theparticles of the composite powder and for the particle sizes d₂₀, d₅₀,d₉₀ also sedimentation analyses are especially beneficial, with the useof a Sedigraph 5100 (Micromeritics GmbH) being especially useful in thiscase. For the particles of the composite powder also particle sizeanalyses by laser diffraction have especially proven themselves, in thiscontext the use of a laser diffraction sensor HELOS/F by Sympatec GmbHbeing especially beneficial. The latter preferably comprises a RODOS drydispersing system.

Incidentally, these indications as well as all other indications givenin the present description refer to a temperature of 23° C., unlessotherwise indicated.

The composite powder according to the invention is comparativelycompact. Of preference, the share of portions inside the particles ofthe composite powder having a density of less than 0.5 g/cm³, especiallyless than 0.25 g/cm³, is less than 10.0%, preferred less than 5.0%,especially less than 1.0%, each related to the total volume of thecomposite powder.

The percentage by weight of the calcium salt particles, preferably thecalcium carbonate particles, preferred of the precipitated calciumcarbonate particles, especially the spherical calcium carbonateparticles, related to the total weight of the composite powder,preferably amounts to at least 0.1 wt.-%, preferred at least 1.0 wt.-%,especially preferred at least 5.0 wt.-%, and expediently is within therange from 5.0 wt.-% to 80.0 wt.-%, especially preferred within therange from 10.0 wt.-% to 60.0 wt.-%, favorably within the range from20.0 wt.-% to 50.0 wt.-%. For calcium salt particles, especially forpreferably spherical calcium carbonate particles which contain, relatedto the total quantity of calcium salt particles, especially ofpreferably spherical calcium carbonate particles, more than 15.0 wt.-%particles having a size of less than 20 μm and/or particles having asize of more than 250 μm, a total quantity of calcium salt particles,especially of preferably spherical calcium carbonate particles withinthe range from 35.0 wt.-% to 45.0 wt.-% has extraordinarily provenitself. For calcium salt particles, especially for preferably sphericalcalcium carbonate particles, which, related to the total quantity ofcalcium salt particles, especially preferably spherical calciumcarbonate particles, contain no more than 15.0 wt.-% of particles havinga size of less than 20 μm and/or particles having a size of more than250 μm, a total quantity of calcium salt particles, especially ofpreferably spherical calcium carbonate particles, within the range from20.0 wt.-% to 30.0 wt.-% has extraordinarily proven itself.

The percentage by weight of the polymer, preferably of the thermoplasticpolymer, related to the total weight of the composition, amounts topreferably at least 0.1 wt.-%, preferred at least 1.0 wt.-%, especiallypreferred at least 5.0 wt.-%, and expediently ranges from 20.0 wt.-% to95 wt.-%, preferred from 40.0 wt.-% to 90.0 wt.-%, favorably from 50.0wt.-% to 80.0 wt.-%.

For a composite powder that contains calcium salt particles, especiallypreferably spherical calcium carbonate particles, which contain, relatedto the total quantity of calcium salt particles, especially ofpreferably spherical calcium carbonate particles, more than 20.0 wt.-%of particles having a size less than 20 μm and/or of particles having asize of more than 250 μm, a total quantity of polymer ranging from 55.0wt.-% to 65.0 wt.-% has extraordinarily proven itself. For a compositepowder that contains calcium salt particles, especially preferablyspherical calcium carbonate particles, which contain, related to thetotal quantity of calcium salt particles, especially of preferablyspherical calcium carbonate particles, no more than 20.0 wt.-% ofparticles having a size of less than 20 μm and/or of particles having asize of more than 250 μm, a total quantity of polymer ranging from 70.0wt.-% to 80.0 wt.-% has particularly proven itself.

The composite powder excels, inter alia, by excellent bonding of thefirst material to the second material. The tight bonding of the firstmaterial to the second material preferably can be verified by mechanicalloading of the composite powder, especially by shaking the compositepowder with non-solvent for the polymer and calcium salt particles,especially for the preferably spherical calcium carbonate particles, at25° C., preferably according to the procedure described in Organikum,17^(th) Edition, VEB Deutscher Verlag der Wissenschaften, Berlin, 1988,Section 2.5.2.1 “Ausschütteln von Lösungen bzw. Suspensionen (Shaking ofsolutions and suspensions)”, pp. 56-57. The shaking time preferably isat least one minute, preferably at least 5 minutes, especially 10minutes, and preferably does not result in a substantial change of form,size and/or composition of the particles of the composite powder.According to the shaking test, especially preferred at least 60 wt.-%,preferably at least 70 wt.-%, preferred at least 80 wt.-%, especiallypreferred at least 90 wt.-%, favorably at least 95 wt.-%, especially atleast 99 wt.-% of the particles of the composite powder are not changedwith respect to their composition, their size and preferably their form.A non-solvent especially suited in this context is water, particularlyfor composite powder containing polyamide.

Furthermore, the particles of the composite powder used according to theinvention usually exhibit a comparatively isotropic particulate formwhich is especially beneficial to applications of the composite powderin SLM methods. The usually almost spherical particulate form of theparticles of the composite powder as a rule results in avoiding or atleast reducing negative influences such as warpage or shrinkage.Consequently, usually also very advantageous melting and solidifyingbehavior of the composite powder can be observed.

In contrast to this, conventional powder particles obtained e.g. bycryogenic grinding have an irregular (amorphous) particulate form withsharp edges and corners. Said powders are not advantageous, however, dueto their detrimental particulate form and, in addition, due to theircomparatively broad particle size distribution and due to theircomparatively high fine fraction of particles of <20 μm for SLM methods.

The calcium salt particles, above all the calcium carbonate particles,especially the precipitated calcium carbonate particles, help tospecifically influence and control the properties of the polymer,especially of the thermoplastic polymer. In this way, the calcium saltparticles, above all the calcium carbonate particles, especially theprecipitated calcium carbonate particles, enable proper buffering and pHstabilization of the polymer, especially of the thermoplastic polymer.Moreover, the biocompatibility of the polymer, especially of thethermoplastic polymer, is significantly improved by the calcium saltparticles, above all by the calcium carbonate particles, especially bythe precipitated calcium carbonate particles. In addition, when theinhibiting calcium carbonate particles are used, significant suppressionof the thermal degradation of the polymer, especially of thethermoplastic polymer, is observed.

The said composite powder may be prepared in a way known per se, forexample by a single-step method, especially by precipitating or coating,preferably by coating with ground material. Furthermore, even aprocedure in which polymer particles are precipitated from a polymersolution which additionally contains small particles in accordance withthe invention, preferably in suspended form, is especially suited.

However, a procedure in which polymer particles and calcium saltparticles, especially preferably spherical calcium carbonate particlesare made to contact one another and are bonded to one another by theaction of mechanical forces has especially proven itself. Appropriately,this is carried out in a suitable mixer or in a mill, especially in animpact mill, pin mill or ultra-rotor mill. The rotor speed preferably ismore than 1 m/s, preferred more than 10 m/s, especially preferred morethan 25 m/s, especially within the range from 50 m/s to 100 m/s.

The temperature at which the composite powder is prepared basically canbe freely selected. However, especially advantageous are temperatures ofmore than −200° C., preferably more than −100° C., preferred more than−50° C., especially preferred more than −20° C., especially more than 0°C. On the other hand, the temperature is advantageously less than 120°C., preferably less than 100° C., preferred less than 70° C., especiallypreferred less than 50° C., especially less than 40° C. Temperaturesranging from more than 0° C. to less than 50° C., especially rangingfrom more than 5° C. to less than 40° C. have extraordinarily proventhemselves.

Within the scope of an especially preferred embodiment of the presentinvention, the mixer or the mill, especially the impact mill, the pinmill or the ultra-rotor mill, is cooled during preparation of thecomposite powder according to the invention to dissipate the energyreleased. Preferably, cooling is effectuated by a coolant having atemperature of less than 25° C., preferred within the range of less than25° C. to −60° C., especially preferred within the range of less than20° C. to −40° C., appropriately within the range of less than 20° C. to−20° C., especially within the range of less than 15° C. to 0° C.Furthermore, the cooling preferably is dimensioned so that at the end ofthe mixing or grinding operation, preferably of the grinding operation,the temperature in the mixing or grinding chamber, especially in thegrinding chamber, is less than 120° C., preferably less than 100° C.,preferred less than 70° C., especially preferred less than 50° C.,especially less than 40° C.

According to an especially preferred embodiment of the presentinvention, this procedure results in the fact, especially forpolyamides, that the calcium salt particles, especially the preferablyspherical calcium carbonate particles, penetrate the interior of thepolymer particles and are preferably completely covered by the polymerso that they are not visible from outside. Such particles may beprocessed and used just as the polymer without the calcium saltparticles, especially just as the polymer without the preferablyspherical calcium carbonate particles, but they exhibit the improvedproperties of the said composite powder.

The composite powder is prepared in accordance with the proceduredescribed in the patent application JP62083029 A. A first material(so-called mother particles) is coated on the surface with a secondmaterial consisting of smaller particles (so-called baby particles). Forthis purpose, preferably a surface modifying device (“hybridizer”) isused comprising a high-speed rotor, a stator and a spherical vesselpreferably comprising inner knives. The use of NARA hybridizationsystems preferably having an outer rotor diameter of 118 mm, especiallyof a hybridization system labeled NHS-0 or NHS-1 by NARA Machinery Co.,Ltd., in this context has especially proven itself.

The mother particles and the baby particles are mixed, preferablydispersed and introduced to the hybridizer. There the mixture ispreferably continued to be dispersed and preferably repeatedly exposedto mechanical forces, especially impact forces, compressing forces,frictional forces and shear forces as well as the mutual interactions ofthe particles to uniformly embed the baby particles into the motherparticles.

Preferred rotor speeds are within the range from 50 m/s to 100 m/s,related to the circumferential speed.

For further details concerning this method, JP62083029 A is referred to,the disclosure of which including the especially appropriate methodvariants is explicitly incorporated in the present application byreference.

Within the scope of another especially preferred variant, the compositepowder is prepared in accordance with the procedure described in thepatent application DE 42 44 254 A1. Accordingly, a method of preparing acomposite powder by affixing a substance onto the surface of athermoplastic material is especially favorable when the thermoplasticmaterial has an average particle diameter of from 100 μm to 10 mm andthe substance has a lower particle diameter and better thermalresistance than the thermoplastic material, especially when the methodcomprises the following steps:

-   -   at first heating the substance having the lower particle        diameter and the better thermal resistance than the        thermoplastic material to a temperature preferably no less than        the softening point of the thermoplastic material during        stirring in an apparatus which preferably includes a stirrer and        a heater;    -   adding the thermoplastic material to the apparatus; and    -   affixing the substance having the better thermal resistance onto        the surface of the thermoplastic material.

For further details concerning this method, DE 42 44 254 A1 is referredto, the disclosure of which including the especially appropriate methodvariants is explicitly incorporated in the present application byreference.

Alternatively, the composite powder is prepared in accordance with theprocedure described in the patent application EP 0 922 488 A1 and/or inthe U.S. Pat. No. 6,403,219 B1. Accordingly, a method of preparing acomposite powder by affixing or bonding fine particles to the surface ofa solid particle acting as a core by making use of impact and thenallowing one or more crystals to grow on the core surface is especiallyadvantageous.

For further details concerning this method, patent application EP 0 922488 A1 and/or U.S. Pat. No. 6,403,219 B1 is/are referred to, thedisclosures of which including the especially appropriate methodvariants are explicitly incorporated in the present application byreference.

The composite powder may be subjected to fixation in accordance with theprocedure described in patent application EP 0 523 372 A1. Thisprocedure is useful especially for a composite powder which was obtainedin accordance with the method described in the patent applicationJP62083029 A. The particles of the composite powder are preferably fixedby thermal plasma spraying, wherein preferably a reduced pressure plasmaspraying device is used which preferably has a capacity of at least 30kW, especially the apparatus described in EP 0 523 372 A1.

For further details concerning this method, patent application EP 0 523372 A1 is referred to, the disclosure of which including the especiallyappropriate method variants is explicitly incorporated in the presentapplication by reference.

The composite powder used in the implant according to the inventionexcels by an excellent property profile suggesting its use especially inlaser sintering methods. Its excellent free-flowing property and itsexcellent flowability during laser sintering enable implants ofexcellent surface quality and surface finish as well as of improvedcomponent density to be produced. At the same time, the composite powderaccording to the invention exhibits very good shrinking behavior as wellas excellent dimensional stability. Moreover, better thermalconductivity can be found outside the laser-treated area.

Moreover, said composite powder exhibits comparatively high isotropywhich enables extremely uniform fusing of the composite powder. Thisbehavior may be utilized in SLM processes for producing components ofhigh quality, high component density, low porosity and a small number ofdefects.

Furthermore, the presence of the calcium salt particles, especially thepreferably spherical calcium carbonate particles, in the compositepowder enables excellent pH stabilization (buffering) in laterapplications, especially in those polymers which contain acid groups orare adapted to release acids under certain conditions. These include,for example, polyvinylchloride and polylactic acid.

Moreover, the said composite powder can possibly replace other moreexpensive materials so as to achieve cost reduction of the finalproduct.

The properties of the composite powder, especially its flowability, canalso be controlled via the moisture of the composite powder and can bespecifically adjusted as needed. On the one hand, the flowability of thecomposite powder basically increases with increasing moisture, thusfacilitating processability of the composite powder. On the other hand,higher moisture of the composite powder may entail thermal degradationor hydrolysis of the polymer as well as process disruptions especiallyin the case of thermal processing of the composite powder primarily inthe presence of impurities and/or in the presence of very fineparticles.

Against this background, the moisture of the said composite powderpreferably is less than 2.5 wt.-%, preferred less than 1.5 wt.-%,especially preferred less than 1.0 wt.-%, even more preferred less than0.9 wt.-%, favorably less than 0.8 wt.-%, expediently less than 0.6wt.-%, particularly preferred less than 0.5 wt.-%, especially less than0.25 wt.-%. On the other hand, the moisture of the said composite powderpreferably is more than 0.000 wt.-%, preferred more than 0.010 wt.-%,especially more than 0.025 wt.-%.

The use of the inhibiting calcium carbonate in this context enables evenfurther improved thermal processability of the composite powder. Theprocessing window (temperature window) once more is definitely largerthan by using conventional calcium carbonate and thermal degradation orhydrolysis of a polymer is once more significantly suppressed.

The desired moisture of the composite powder can be achieved bypre-drying of the composite powder known per se prior to processing,with drying being basically recommended in the production process. Forstable process control in this context drying up to a moisture contentranging from 0.01 wt.-% to 0.1 wt.-% has turned out to be especiallyfavorable. Furthermore, the use of a microwave vacuum drier hasespecially proven itself.

The composite powder may be further processed in a comparatively simplemanner as now only one component (the composite powder) and no longertwo components (calcium salt particles, especially preferably sphericalcalcium carbonate particles, and polymer) have to be processed. Problemsof dispersion are not observed due to the tight bonding between thepolymer and the calcium salt particles, especially the preferablyspherical calcium carbonate particles.

Furthermore, the microstructure, the melting behavior and the flowbehavior of the composite powder can be specifically controlled by theselection of the fractions and the size of the respective singlecomponents. Said properties of the composite powder can be exploited, inturn, to specifically control the final structure of the resultingimplants, especially the biocompatibility, the biodegradability and themechanical properties thereof.

An addition of further processing aids, especially of specific solvents,usually is not required for processing the composite powder. Thisexpands the possible fields of application of the composition especiallyin the pharmaceutical and food sectors.

The composite powder can be directly used as such. Due to its excellentproperty profile, the composite powder is especially suited, however, asan additive, especially preferred as a polymer additive, as an additionor starting material for compounding, for the production of implants,for applications in medical engineering and/or in microtechnology and/orfor the production of foamed implants. Especially preferred applicationsin medical engineering include preferably absorbable implants.Especially expedient fields of application comprise injection-moldedscrews, pressed plates, especially melt-pressed plates, foamed implantsas well as flowable powders for selective production methods, in thelatter case the total particle size of the particles of the compositepowder being preferably less than 3 mm and preferably more than 5.0 μm.

In the form of a polymer additive, the composite powder is preferablyadded to at least one polymer, especially to a thermoplastic polymer, asmatrix polymer. In this case, the polymers which can also be used as acomponent of the composite powder are especially preferred. To avoidrepetitions, therefore the foregoing statements are referred to,especially as regards the preferred forms of the polymer.Extraordinarily preferred matrix polymers include polyvinylchloride(PVC), polyurethane (PU), silicone, polypropylene (PP), polyethylene(PE), especially UHMWPE, and polylactic acid (PLA).

The matrix polymer and the polymer of the composite powder canpreferably be mixed at the temperature of use, and especially preferredare chemically identical.

Especially preferred compositions contain 40.0 wt.-% to 99.9 wt.-%, ofat least one matrix polymer and 0.1 wt.-% to 50.0 wt.-% of at least onesaid composite powder.

The production of the composition may be carried out in a manner knownper se by mixing the components.

The composition then can be further processed in the usual way,especially granulated, ground, extruded, injection-molded, foamed orelse used in 3D printing methods.

Furthermore, the composite powder can be further processed and/or useddirectly, i.e. without addition of additional polymers.

The advantages of the composite powder can be observed especially whengranulating, extruding, injection-molding, melt-pressing, foaming and/or3D printing the composite powder.

Polymer foams are preferably produced by generating or introducing agaseous phase to a composition comprising the composite powder and atleast one matrix polymer, where necessary. It is the objective todistribute the gas as uniformly as possible within the composition so asto obtain a uniform and homogeneous foam structure. The gas may beintroduced in various ways.

Of preference, the gaseous phase is generated by adding a blowing agent.Blowing agents are substances which release gases by chemical reactions(chemical blowing agents) or by phase transition (physical blowingagents). In foam extrusion or in foam injection molding the chemicalblowing agent is admixed to the composition in the form of a masterbatchor a physical blowing agent is injected under pressure directly into themelt of the composition. The injection is referred to as direct gassingand is used especially in processing thermoplastic polymers.

Moreover, the said composite powder per se is suited especially forproducing implants adapted to replace conventional implants made frommetal in the case of bone fractures. The implants serve for fixing thebones until the fracture has healed up. While implants of metal arenormally retained in the body or have to be removed by furtheroperation, the implants obtainable from the composite powder accordingto the invention act as temporary aids. They expediently comprisepolymers which the body itself can degrade and substances which providecalcium and valuable phosphorus substances for osteogenesis. Theadvantages resulting for the patient are obvious: no further operationfor removing the implant and accelerated regeneration of the bones.

According to an especially preferred variant of the present invention,the said composite powder is used for producing implants by selectivelaser sintering. Expediently, particles of the composite powderaccording to the invention tightly packed next to one another to form apowder bed are locally slightly surface-fused or melted (the polymeronly) with the aid of a laser-scanner unit, a directly deflectedelectron beam or an infrared heating having a mask depicting thegeometry. They solidify by cooling due to heat conduction and thuscombine to form a solid layer. The powder granules that are notsurface-fused remain as supporting material within the component and arepreferably removed after completion of the building process. By repeatedcoating with powder, analogously to the first layer further layers canbe solidified and bonded to the first layer.

Types of lasers especially suited for laser sintering methods are allthose which cause the polymer of the composite powder according to theinvention to sinter, to melt or to crosslink, especially CO₂ lasers (10μm), ND-YAG lasers (1,060 nm), He—Ne lasers (633 nm) or dye lasers(350-1,000 nm). Preferably, a CO₂ laser is used.

The energy density in the filling during radiation preferably rangesfrom 0.1 J/mm³ to 10 J/mm³.

The active diameter of the laser beam preferably ranges from 0.01 nm to0.5 nm, preferably 0.1 nm to 0.5 nm, depending on the application.

Of preference, pulsed lasers are used, wherein a high pulse frequency,especially from 1 kHz to 100 kHz, has turned out to be particularlysuited.

The preferred process can be described as follows: The laser beam isincident on the uppermost layer of the filling of said material to beused according to the invention and, in so doing, sinters the materialat a predetermined layer thickness. Said layer thickness may be from0.01 mm to 1 mm, preferably from 0.05 mm to 0.5 mm. In this way, thefirst layer of the desired implant is produced. Subsequently, theworking space is lowered by an amount which is less than the thicknessof the sintered layer. The working space is filled up to the originalheight with additional polymer material. By repeated radiation with thelaser, the second layer of the implant is sintered and bonded to thepreceding layer. By repeating the operation, the further layers areproduced until the implant is completed.

The exposure rate during laser scanning preferably amounts to 1 mm/s to1,000 mm/s. Typically, a rate of about 100 mm/s is applied.

In the present case, for surface-fusing or melting the polymer it hasespecially proven itself to heat to a temperature within the range from60° C. to 250° C., preferably within the range from 100° C. to 230° C.,especially within the range from 150° C. to 200° C.

The subject matter of the present invention further are implants whichare obtainable by selective laser sintering of a composition comprisingsaid composite powder, wherein implants for applications in the field ofneuro, oral, maxillary, facial, ear, nose and throat surgery as well ashand, foot, thorax, costal and shoulder surgery are especiallypreferred.

The percentage of the said composite powder in the composition ispreferably at least 50.0 wt.-%, preferred at least 75.0 wt.-%,especially preferred at least 90 wt.-%, especially at least 99.0 wt.-%.Within the scope of a particular embodiment of the present invention,the composition contains exclusively the composite powder according tothe invention.

The implants according to the invention appropriately excel by thefollowing properties:

-   -   excellent surface quality,    -   excellent surface finish,    -   excellent component density, preferably more than 95%,        especially more than 97%,    -   excellent shrinking behavior,    -   excellent dimensional stability,    -   very few defects,    -   very low porosity,    -   very low content of degradation products,    -   excellent three-point flexural strength, preferably more than 60        MPa, especially preferred more than 65 MPa, especially more than        70 MPa,    -   excellent elasticity modulus, preferably of 3420 N/mm²,        especially preferred of more than 3750 N/mm², favorably of more        than 4000 N/mm², especially of more than 4500 N/mm²,    -   excellent pH stability,    -   excellent biocompatibility,    -   excellent osteo-conduction,    -   excellent absorbing capacity,    -   excellent biodegradability.

Hereinafter, the present invention shall be further illustrated byplural examples and comparative examples without the inventive ideabeing intended to be limited in this way.

-   -   Materials used:    -   granulate 1 (poly(L-lactide); inherent viscosity: 0.8-1.2 dl/g        (0.1% in chloroform, 25° C.); Tg: 60-65° C.; Tm: 180-185° C.)    -   granulate 2 (poly(L-lactide); inherent viscosity 1.5-2.0 dl/g        (0.1% in chloroform; 25° C.)); Tg: 60-65° C.;    -   granulate 3 (poly(D,L-lactide); inherent viscosity 1.8-2.2 dl/g        (0.1% in chloroform; 25° C.)); Tg: 55-60° C.; amorphous polymer        without melting point

The mean particle diameter of each of the polylactide granulates 1 to 3was within the range from 1 to 6 mm.

Within the scope of the present examples, the following variables wereestablished as follows:

-   -   CaCO₃ content: The CaCO₃ content was established by means of        thermogravimetry by a STA 6000 by Perkin Elmer under nitrogen        within the range from 40° C. to 1000° C. at a heating rate of        20° C./min. The weight loss was determined between about 550° C.        and 1000° C. and therefrom the CaCO₃ content was calculated in        percent through the factor 2.274 (molar mass ratio CaCO₃: CO₂).    -   β-tricalcium phosphate content (β-TCP content): The β-TCP        content was established by means of thermogravimetry by a STA        6000 by Perkin Elmer under nitrogen within the range from 40° C.        to 1000° C. at a heating rate of 20° C./min. The weight        percentage retained at 1000° C. corresponds to the β-TCP content        in percent.    -   T_(P): The peak temperature T_(P) was established by means of        thermogravimetry by a STA 6000 by Perkin Elmer under nitrogen        within the range from 40° C. to 1000° C. at a heating rate of        20° C./min. The peak temperature of the first derivation of the        mass loss curve corresponds to the temperature with the maximum        mass loss during polymer degradation.    -   d₂₀, d₅₀, d₉₀: The grain size distribution of the calcium        carbonate-containing composite powder was determined by laser        diffraction (HELOS measuring range R5 with RODOS dispersing        system by Sympatec). The grain size distribution was determined        for the calcium carbonate powder by the Sedigraph 5100 with        Master Tech 51 by Micromeretics. The dispersing solution used        was 0.1% sodium polyphosphate solution (NPP).    -   Fraction <20 μm: determination analogously to d₅₀. Evaluation of        the fraction <20 μm.    -   Moisture: The water content of the calcium carbonate containing        composite powder was determined by Karl Fischer Coulometer C30        by Mettler Toledo at 150° C. The water content of the calcium        carbonate powders was determined by the halogen-moisture        analyzer HB43 by Mettler at 130° C. (weighted sample: 6.4-8.6 g        of powder; measurement time: 8 minutes).    -   Inherent viscosity: The inherent viscosity (dl/g) was determined        by Ubbelohde Viscosimeter Kapillare 0c in chloroform at 25° C.        and 0.1% of polymer concentration.    -   Flowability: The flowability of the samples was judged by an        electromotive film applicator by Erichsen. A 200 μm and, resp.,        500 μm doctor blade was used for this purpose. The application        rate to the foil type 255 (Leneta) was 12.5 mm/s. Rating as        follows: 1=excellent, 2=good, 3=satisfactory; 4=sufficient;        5=poor

Determination of the mechanical properties at injection-moldedspecimens: Three-point flexural strength and E modulus were determinedby means of Texture Analyser TA.XTPlus (Stable Micro Systems, Godalming(UK)). The capacity of the load cell used was 50 kg. Exponent 6.1.9.0software was used. The details of measurement are shown in the followingTable 1:

TABLE 1 Load means: three-point load under DIN EN 843-1 diameter ofsupport/load rolls: 5.0 mm Measurement: in accordance with DIN EN ISO178 support distance: 45.0 mm testing speed: 0.02 mm/s preliminaryspeed: 0.03 mm/s force/path recording Specimens: dimensions about 3 mm ×10 mm × 50 mm after production (injection molding) storing untilmeasurement in exsiccator at room temperature n ≥ 5

Specimens were produced by HAAKE MiniLab II extruder and, resp.,injection molding by HAAKE MiniJet II. The process conditions forspecimen production are listed in the following Table 2:

TABLE 2 Temper- Temper- Temper- ature ature Pressure Time atureinjection- injection injection injection Extruder molding mold moldingmolding Composite [° C.] [° C.] [° C.] [bars] [s] Example 3 180 180 80700 10 Example 4 180 180 70 700 10 Example 5 185 185 80 700 10 Example 6195 195 80 700 10 Example 7 175 175 72 700 10 Comparison 175 175 70 70010 1

Cytotoxicity Test

The cytotoxicity test (FDA/GelRed) was carried out as follows:

The reference and, resp., negative control used was Tissue CulturePolystyrene (TCPS). 4 replicates were used for each sample and four TCPS(4×) were used for control.

Test Procedure:

-   1. The non-sterile samples were made available in a 24 well    microtiter plate. In the same, the samples as well as the TCPS    plates were sterilized (undenatured) with 70% ethanol, then for 2×30    min rinsed with 1×PBS (phosphate-buffered saline solution) and after    that equilibrated with sterile a medium. Then the samples were    inoculated with MC3T3-E1 cells of inoculation coverage of 25,000    cells/cm² (50,000 cells/ml).

A partial medium exchange (1:2) took place on day 2.

-   2. After 1 and 4 days in cell culture the cytotoxicity was    determined.-   3. Vital staining was carried out on day 1 and 4 according to    standard protocol by means of combined staining of FDA and GelRed.-   4. The microscopic images were produced at the Observer Z1m/LSM 700.

Lens: EC Plan-Neofluar 10×;

Images taken by the camera AxioCam HRc:Excitation of green fluorescence: LED Colibri 470; filter set FS10(AF488)Excitation of red fluorescence: LED Colibri 530; filter set FS14 (AF546)Images scanned in the laser scan mode:Track 1: laser: 488 nm, DBS 560 nm, PMT1: 488-560 nm,Track 2: laser 555 nm, DBS 565 nm, PMT2: 565-800 nm

-   5. Evaluation was made according to the following cytotoxicity    scale:    Acceptance: the material is not cytotoxic (max. 5% of dead cells)    Slight inhibition: the material is slightly toxic (5%-20% of dead    cells)    Significant inhibition: the material is moderately toxic (20%-50% of    dead cells)    Toxicity: the material is highly cytotoxic (>50%-100% dead cells)-   6. The cell numbers relate to the image detail taken or scanned.

The results are listed in Table 3.

Electron Microscope (SEM)

The SEM images were taken by a high-voltage electron microscope (Zeiss,DSM 962) at 15 kV. The samples were sprayed with a gold-palladium layer.

EXAMPLE 1

A CO₂ gas mixture containing 20% of CO₂ and 80% of N₂ was introduced to4 l of calcium hydroxide suspension having a concentration of 75 WI CaOat an initial temperature of 10° C. The gas flow was 300 I/h. Thereaction mixture was stirred at 350 rpm and the reaction heat wasdissipated during reaction. Upon abrupt drop of the conductance (drop ofmore than 0.5 mS/cm/min and decrease of the conductance by more than0.25 mS/cm within 30 seconds) 0.7% of amino tri(methylene phosphonicacid), based on CaO (as theoretical reference value) is added to thesuspension. The reaction into the spherical calcium carbonate particleswas completed when the reaction mixture was carbonated quantitativelyinto spherical calcium carbonate particles, wherein the reaction mixturethen showed a pH value between 7 and 9. In the present case, thereaction was completed after about 2 h and the reaction mixture had a pHvalue of 7 at the reaction end.

The resulting spherical calcium carbonate particles were separated anddried in a conventional way. They showed a mean particle diameter of 12μm. A typical SEM image is shown in FIG. 1.

EXAMPLE 2

500 ml of VE (demineralized) water were provided in a 1000 ml beaker.125 g of spherical calcium carbonate particles according to Example 1were added under stirring and the resulting mixture was stirred for 5min. 37.5 g of a 10% sodium metaphosphate (NaPO₃)_(n) solution wereslowly added and the resulting mixture was stirred for 10 min. 75.0 g of10% phosphoric acid were slowly added and the resulting mixture wasstirred for 20 h. The precipitation is separated and dried in the dryingcabinet over night at 130° C. The resulting spherical calcium carbonateparticles equally had a mean particle diameter of 12 μm.

A SEM image of the spherical calcium carbonate particles is shown inFIG. 2. On the surface of the spherical calcium carbonate particles athin phosphate layer is visible.

EXAMPLE 3

A composite powder of spherical calcium carbonate particles and apolylactide (PLLA) was prepared in accordance with the method describedin JP 62083029 A using the NHS-1 apparatus. It was cooled with water at12° C. A polylactide granulate 1 was used as mother particles and thespherical calcium carbonate particles of Example 1 were used as the babyparticles (filler).

39.5 g of polylactide granulate were mixed with 26.3 g CaCO₃ powder andfilled at 6.400 rpm. The rotor speed of the unit was set to 6.400 rpm(80 m/s) and the metered materials were processed for 10 min. Themaximum temperature reached in the grinding chamber of NHS-1 was 35° C.A total of 7 repetitions were carried out with equal material quantitiesand machine settings. A total of 449 g of composite powder was obtained.The composite powder obtained was manually dry-sieved through a 250 μmsieve. The sieve residue (fraction >250 μm) was 0.4%.

A SEM image of the composite powder obtained is shown in FIG. 3 a.

EXAMPLES 4 TO 7

Further composite powders were prepared analogously to Example 3,wherein in Example 5 cooling took place at about 20° C. In each case 30g of polylactide granulate were mixed with 20 g of CaCO₃ powder. Themaximum temperature reached within the grinding chamber of NHS-1 was 33°C. for Example 4, 58° C. for Example 5, 35° C. for Example 6 and 35° C.for Example 7. The products were sieved to remove the coursefraction >250 μm where possible (manual dry sieving through 250 μmsieve). In the Examples 4, 6 and 7, additionally the fraction <20 μm wasclassified by flow where possible (by means of air separation) or bysieving (by means of air jet sieving machine). The materials used, theimplementation of preparation with or without sieving/air separation aswell as the properties of the composite powders obtained are listed inthe following Table 3.

FIG. 3a , FIG. 3b and FIG. 3c illustrate a SEM image of Example 3 andimages of plural doctor blade applications (12.5 mm/s) of Example 3(FIG. 3 b: 200 μm doctor blade; FIG. 3 c: 500 μm doctor blade).

The SEM image of the composite powder obtained is shown in FIG. 3a . Incontrast to the edgy irregular particulate form which is typical of thecryogenically ground powders, the particles of the composite powderobtained show a round particulate form and, resp., high sphericity veryadvantageous to SLM methods. The PLLA surface is sparsely occupied withspherical calcium carbonate particles and fragments thereof. The samplehas a definitely smaller particle size distribution having increasedfine fraction.

The powder is flowable to a restricted extent (FIGS. 3b and 3c ). Apowder heap is pushed along in front of the doctor blade. The restrictedflow behavior, probably caused by a higher fraction of fine particles,causes only very thin layers to be formed by both doctor blades.

FIG. 4a , FIG. 4b and FIG. 4c illustrate a SEM image of Example 4 aswell as images of plural doctor blade applications (12.5 mm/s) ofExample 4 (FIG. 4 b: 200 μm doctor blade; FIG. 4 c: 500 μm doctorblade).

The SEM image of the composite powder obtained is shown in FIG. 4a . Incontrast to the edgy irregular particulate form which is typical of thecryogenically ground powders, the particles of the composite powderobtained show a round particulate form and, resp., high sphericity veryadvantageous to SLM methods. The PLLA surface is sparsely occupied withspherical calcium carbonate particles and fragments thereof. The sampleexhibits a definitely smaller particle size distribution having a smallfine fraction.

The powder is properly flowable and applicable (FIGS. 4b and 4c ). Thethin layers (200 μm), too, can be applied and are largely free fromdoctor streaks (tracking grooves).

The powder layer applied with 500 μm is homogeneous, densely packed,smooth and free from doctor streaks.

FIG. 5a , FIG. 5b and FIG. 5c illustrate a SEM image of Example 5 aswell as images of several applications (12.5 mm/s) of Example 5 (FIG. 5b: 200 μm doctor blade; FIG. 5 c: 500 μm doctor blade). The powder isflowable to a restricted extent. A powder heap is pushed along by thedoctor blade. Due to the restricted flow behavior, probably caused by ahigher fraction of fine particles, only very thin layers are formed byboth doctor blades.

FIG. 6a , FIG. 6b and FIG. 6c illustrate a SEM image of Example 6 aswell as images of plural applications (12.5 mm/s) of Example 6 (FIG. 6b: 200 μm doctor blade; FIG. 6 c: 500 μm doctor blade). The powder isproperly flowable and applicable. The thin layers (200 μm), too, can beapplied. Individual doctor streaks caused by probably too coarse powderparticles are visible. The powder layer applied by 500 μm is not quitedensely packed but is free from doctor streaks.

FIG. 7a , FIG. 7b and FIG. 7c illustrate a SEM image of Example 7 aswell as images of plural applications (12.5 mm/s) of Example 7 (FIG. 7b: 200 μm doctor blade; FIG. 7 c: 500 μm doctor blade). The powder isflowable and applicable. The thin layers (200 μm), too, can be applied.They are not homogeneous and are increasingly interspersed with doctorstreaks. Somewhat restricted flow behavior is probably caused by toocoarse powder particles. The powder layer applied with 500 μm ishomogeneous and free from doctor streaks.

Comparison 1

Microstructured composite particles of spherical calcium carbonateparticles of Example 1 and an amorphous polylactide (PDLLA) wereprepared in accordance with the method described in JP 62083029 A usingthe NHS-1 apparatus. It was cooled with water at 12° C. A polylactidegranulate 3 was used as mother particles and the spherical calciumcarbonate particles of Example 1 were used as the baby particles.

39.5 g of polylactide granulate were mixed with 10.5 g of CaCO₃ powderand filled at 8,000 rpm. The rotor speed of the unit was set to 8,000rpm (100 m/s) and the metered materials were processed for 1.5 min. Themaximum temperature reached within the grinding chamber of the NHS-1 was71° C. A total of 49 repetitions was carried out with equal materialquantities and machine settings. A total of 2376 g of structuredcomposite particles were obtained. The obtained structured compositeparticles were manually dry-sieved through an 800 μm sieve for measuringthe particle size distribution. The sieve residue (fraction >800 μm)amounted to 47%.

The properties of the microstructured composite particles obtained arelisted in the following Table 3.

FIG. 8a , FIG. 8b and FIG. 8c illustrate a SEM image of Comparison 1 aswell as images of plural applications (12.5 mm/s) of Comparison 1 (FIG.8 b: 200 μm doctor blade; FIG. 8 c: 500 μm doctor blade). The powder ispoorly flowable and cannot be applied to form layer thicknesses of 200and, resp., 500 μm thickness. The too coarse irregular particles getjammed during application. Non-homogeneous layers having very frequentand distinct doctor streaks are formed.

The SEM analysis illustrates that the surfaces of the structuredcomposite particles are sparsely occupied with spherical calciumcarbonate particles and the fragments thereof. As compared to theExamples 3 to 7, the particles show a more irregular particle geometry.

EXAMPLE 8

A composite powder of 6-tricalcium phosphate particles and a polylactide(PDLLA) was prepared in accordance with the method described in JP62083029 A using the NHS-1 apparatus. It was cooled with water at 12° C.A polylactide granulate 3 was used as mother particles and 6-tricalciumphosphate (β-TCP; d₂₀=30 μm; d₅₀=141 μm; d₉₀=544 μm) was used as babyparticles. The SEM image of the β-TCP used is shown in FIG. 9a and FIG.9 b.

30.0 g of polylactide granulate were mixed with 20.0 g of β-TCP powderand were filled at 6,400 rpm. The rotor speed of the unit was set to6,400 rpm (80 m/s) and the metered materials were processed for 10 min.A total of 5 repetitions with equal material quantities and machinesettings was carried out. A total of 249 g of composite powder wasobtained. The product was sieved to remove the coarse fraction >250 μmwhere possible (manual dry-sieving through a 250 μm sieve). Then thefine fraction <20 μm was separated through a 20 μm sieve by means of anair jet sieving machine.

EXAMPLE 9

A composite powder of rhombohedral calcium carbonate particles and apolylactide (PDLLA) was prepared in accordance with the method describedin JP 62083029 A using the NHS-1 apparatus. It was cooled with water at12° C. A polylactide granulate 3 was used as mother particles andrhombohedral calcium carbonate particles (d₂₀=11 μm; d₅₀=16 μm; d₉₀=32μm) were used as baby particles.

30.0 g of polylactide granulate were mixed with 20.0 g of therhombohedral calcium carbonate particles and were filled at 6,400 rpm.The rotor speed of the unit was set to 6,400 rpm (80 m/s) and themetered materials were processed for 10 min. A total of 5 repetitionswith equal material quantities and machine settings was carried out. Atotal of 232 g of composite powder was obtained. The product was sievedto remove the coarse fraction >250 μm where possible (manual dry-sievingthrough a 250 μm sieve). Then the fine fraction <20 μm was separatedthrough a 20 μm sieve by means of an air jet sieving machine.

EXAMPLE 10

A composite powder of ground calcium carbonate particles and apolylactide (PDLLA) was prepared in accordance with the method describedin JP 62083029 A using the NHS-1 apparatus. It was cooled with water at12° C. A polylactide granulate 3 was used as mother particles and groundcalcium carbonate (GCC; d₂₀=15 μm; d₅₀=46 μm; d₉₀=146 μm) were used asbaby particles.

30.0 g of polylactide granulate were mixed with 20.0 g of GCC and werefilled at 6,400 rpm. The rotor speed of the unit was set to 6,400 rpm(80 m/s) and the metered materials were processed for 10 min. A total of5 repetitions with equal material quantities and machine settings wascarried out. A total of 247 g of composite powder was obtained. Theproduct was sieved to remove the coarse fraction >250 μm where possible(manual dry-sieving through a 250 μm sieve). Then the fine fraction <20μm was separated through a 20 μm sieve by means of an air jet sievingmachine.

TABLE 3 Example 3 Example 4 Example 5 Example 6 Example 7 Comparison 1Composition for the preparation of the composite powder withmicrostructured particles m(Example 1) 40 40 0 40 40 20 [wt.-%]m(Example 2) 0 0 40 0 0 0 [wt.-%] polylactide granulate 1 granulate 1granulate 1 granulate 2 granulate 3 granulate 3 m(polylactide) 60 60 6060 60 80 [wt.-%] Preparation of the composite powder withmicrostructured particles sieving <250 μm <250 μm <250 μm <250 μm <250μm <800 μm <20 μm <20 μm <20 μm (for measurement (air separation) (airjet (air jet of particle size sieving) sieving) distribution only) CaCO₃content 41.1 22.4 35.0 19.5 22.3 22.4 [wt.-%]¹ (mean value from 5measurements) T_(P) [° C.]¹ 291 310 341 304 286 319 (mean value from 5measurements) d₅₀ [μm]¹ 25 47 26 112 136 228 share <20 μm 43.6 13.7 37.70.3 2.3 20.6 [vol %]¹ d₂₀ [μm]¹ 9 26 14 69 80 d₉₀ [μm]¹ 86 102 70 223247 d₂₀/d₅₀ [%] 36 52 54 62 59 moisture 0.8 0.6 0.5 0.9 0.9 0.3 [wt.-%]¹inherent 1.0 1.0 0.9 1.9 1.9 1.9 viscosity [dl/g] three-point 66 68 7784 67 79 flexural strength [MPa] E modulus 4782 3901 4518 3530 3594 3420[N/mm²] flowability 4 1 4 2 3 5 cytotoxicity test non-cytotoxicnon-cytotoxic non-cytotoxic — non-cytotoxic non-cytotoxic Example 8Example 9 Example 10 Composition for the preparation of the compositepowder with microstructured particles m(filler) [wt.-%] 40 40 40polylactide granulate 3 granulate 3 granulate 3 m(polylactide) 60 60 60[wt.-%] Preparation of the composite powder with microstructuredparticles sieving <250 μm <250 μm <250 μm <20 μm <20 μm <20 μm Air jetsieving Air jet sieving Air jet sieving filler content 24.9 24.2 26.6[wt.-%]* T_(P) [° C.] 341° C. 303° C. 303° C. d₂₀ [μm] 85 74 75 d₅₀ [μm]131 128 120 d₉₀ [μm] 226 257 230 fraction <20 μm 3.0 4.5 1.6 [vol %]moisture [wt.-%] 0.6 0.6 0.6 inherent viscosity 1.8 1.8 1.8 [dl/g] ¹Atleast double-determination

1. Method for manufacturing an implant using a composite powder withmicrostructured particles, wherein initially the composite powder isobtained by bonding large particles to small particles, wherein thelarge particles have a mean particle diameter in the range from 10 μm to10 mm, the large particles comprise at least one polymer, the smallparticles are arranged on the surface of the large particles and/or arenon-homogeneously spread within the large particles, the small particlescomprise a calcium salt, the small particles have a mean particle sizein the range from 0.01 μm to 1.0 mm, and wherein subsequently theimplant is formed by selective laser sintering of a compositioncomprising the composite powder, characterized in that the particles ofthe composite powder have a mean particle size d₅₀ in the range from 10μm to less than 200 μm and the fine fraction of the composite powder isless than 50 vol %.
 2. The method according to claim 1, characterized inthat the particles of the composite powder have a particle size d₉₀ ofless than 350 μm.
 3. The method according to claim 1, characterized inthat the particles of the composite powder have an average particle sized₅₀ within the range from 20 μm to less than 150 μm.
 4. The methodaccording to claim 1, characterized in that the particles of thecomposite powder have a d₂₀/d₅₀ ratio of less than 100% and/or that thecalcium salt has an aspect ratio of less than 5 and/or that the calciumsalt comprises spherical calcium carbonate and/or that the calcium saltcomprises calcium phosphate.
 5. The method according to claim 1,characterized in that the large particles comprise at least onethermoplastic polymer.
 6. The method according to claim 1, characterizedin that the large particles comprise at least one absorbable polymer. 7.The method according to claim 6, characterized in that the absorbablepolymer has an inherent viscosity, measured in chloroform at 25° C.,0.1% polymer concentration, within the range from 0.3 dl/g to 8.0 dl/g.8. The method implant according to claim 1, characterized in that thelarge particles comprise poly-D, poly-L and/or poly-D,L-lactic acid. 9.The method according to claim 1, characterized in that the largeparticles comprise at least one absorbable polyester having a numberaverage molecular weight in the range from 500 g/mol to 1,000,000 g/mol.10. The method according to claim 1, characterized in that the largeparticles comprise at least one polyamide.
 11. The method according toclaim 1, characterized in that the large particles comprise at least onepolyurethane.
 12. The method according to claim 1, characterized in thatthe percentage by weight of the calcium salt particle, related to thetotal weight of the composite powder, is at least 0.1 wt.-%.
 13. Themethod implant according to claim 1, characterized in that the compositepowder, related to the total weight of the composite powder, comprises40.0 wt.-% to 80.0 wt.-% of PLLA and 20.0 wt.-% to 60.0 wt.-% of calciumcarbonate particles.
 14. (canceled)